SUMMARY
Many advances in understanding colorectal cancer heterogeneity and its impact on the variability of treatment efficacy have been achieved in recent
years. New methods have also been introduced in colorectal cancer diagnosis and early detection, including molecular biology techniques as well as
newly developed or improved imaging techniques. We are currently aware of some aspects of colorectal cancer heterogeneity, such as alterations in the
epidermal growth factor receptor signalling or the different behaviours of tumours belonging to different genetic and epigenetic subtypes. In the
future, greater attention should also be focused on other signalling circuits with the goal to treat patients individually, based on the
characteristics of their tumours. This so-called personalised medicine will bring more benefits to patients, without unnecessary adverse side effects.
Therefore, all new information regarding colorectal cancer biology brings us one step closer to accomplishing this goal.
KEY WORDS
colorectal cancer; chromosomal instability; microsatellite instability; CpG island methylator phenotype; EGFR pathway; circulating tumour cells; stool
DNA
REFERENCES
Ahlquist DA. Next-generation stool DNA testing: expanding the scope. Gastroenterology. 136: 2068-2073, 2009.
[CrossRef]
[PubMed]
Ahlquist DA. Molecular detection of colorectal neoplasia. Gastroenterology. 138: 2127-2139, 2010.
[CrossRef]
[PubMed]
Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all
major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 10: 6897-6904, 2004.
[CrossRef]
[PubMed]
Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is
required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 26: 1626-1634, 2008.
[CrossRef]
[PubMed]
Ang PW, Loh M, Liem N, Lim PL, Grieu F, Vaithilingam A, Platell C, Yong WP, Iacopetta B, Soong R. Comprehensive profiling of DNA methylation in
colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer. 10: 227, 2010.
[CrossRef]
[PubMed]
Antolovic D, Galindo L, Carstens A, Rahbari N, Buchler MW, Weitz J, Koch M. Heterogeneous detection of circulating tumor cells in patients with
colorectal cancer by immunomagnetic enrichment using different EpCAM-specific antibodies. BMC Biotechnol. 10: 35, 2010.
[CrossRef]
[PubMed]
Armaghany T, Wilson JD, Chu Q, Mills G. Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 5: 19-27, 2012.
[PubMed]
Bae JM, Kim MJ, Kim JH, Koh JM, Cho NY, Kim TY, Kang GH. Differential clinicopathological features in microsatellite instability-positive colorectal
cancers depending on CIMP status. Virchows Arch. 459: 55-63, 2011.
[CrossRef]
[PubMed]
Bidard FC, Ferrand FR, Huguet F, Hammel P, Louvet C, Malka D, Boige V, Ducreux M, Andre T, de Gramont A, Mariani P, Pierga JY. Disseminated and
circulating tumor cells in gastrointestinal oncology. Crit Rev Oncol Hematol. 82: 103-115, 2012.
[CrossRef]
[PubMed]
Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A et al. Fluorouracil,
leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 27: 663-671,
2009.
[CrossRef]
[PubMed]
Bokemeyer C, Cutsem EV, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Kohne CH. Addition of cetuximab to chemotherapy as first-line
treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 48:
1466-1475, 2012.
[CrossRef]
[PubMed]
Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 138: 2073-2087, 2010.
[CrossRef]
[PubMed]
Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S. A National
Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for
the determination of microsatellite instability in colorectal cancer. Cancer Res. 58: 5248-5257, 1998.
[PubMed]
Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487: 330-337, 2012.
[CrossRef]
[PubMed]
Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H et al. Relationship of
circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin
Oncol. 26: 3213-3221, 2008.
[CrossRef]
[PubMed]
Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, Karakayali H, Haberal M. Clinicopathological significance of PTEN loss and the
phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? Am J Surg. 195: 719-725, 2008.
[CrossRef]
[PubMed]
Cotton AM, Lam L, Affleck JG, Wilson IM, Pe?aherrera MS, McFadden DE, Kobor MS, Lam WL, Robinson WP, Brown CJ. Chromosome-wide DNA methylation
analysis predicts human tissue-specific X inactivation. Hum Genet. 130: 187-201, 2011.
[CrossRef]
[PubMed]
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab
monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 351: 337-345, 2004.
[CrossRef]
[PubMed]
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E et al. Mutations of the
BRAF gene in human cancer. Nature. 417: 949-954, 2002.
[CrossRef]
[PubMed]
De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar
S. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann
Oncol. 19: 508-515, 2008.
[CrossRef]
[PubMed]
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F,
Rougier P et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory
metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11: 753-762, 2010a.
[CrossRef]
De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O’Callaghan CJ
et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.
JAMA. 304: 1812-1820, 2010b.
[CrossRef]
[PubMed]
Deng L, Qi Z, Zou B, Wu H, Huang H, Kajiyama T, Kambara H, Zhou G. Digital detection of multiple minority mutants in stool DNA for noninvasive
colorectal cancer diagnosis. Anal Chem. 84: 5645-5652, 2012.
[CrossRef]
[PubMed]
Des Guetz G, Uzzan B, Nicolas P, Schischmanoff O, Perret GY, Morere JF. Microsatellite instability does not predict the efficacy of chemotherapy in
metastatic colorectal cancer. A systematic review and meta-analysis. Anticancer Res. 29: 1615-1620, 2009.
[PubMed]
Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A.
Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectalcancer. J Clin Oncol. 26: 5705-5712, 2008.
[CrossRef]
[PubMed]
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA, Jr. Circulating
mutant DNA to assess tumor dynamics. Nat Med. 14: 985-990, 2008.
[CrossRef]
[PubMed]
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I et al.
Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line
treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 28: 4697-4705, 2010.
[CrossRef]
[PubMed]
Elliott GO, Johnson IT, Scarll J, Dainty J, Williams EA, Garg D, Coupe A, Bradburn DM, Mathers JC, Belshaw NJ. Quantitative profiling of CpG island
methylation in human stool for colorectal cancer detection. Int J Colorectal Dis. 28: 35-42, 2013.
[CrossRef]
[PubMed]
Fallik D, Borrini F, Boige V, Viguier J, Jacob S, Miquel C, Sabourin JC, Ducreux M, Praz F. Microsatellite instability is a predictive factor of the
tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 63: 5738-5744, 2003.
[PubMed]
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 61: 759-767, 1990.
[CrossRef]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:
2893-2917, 2010.
[CrossRef]
[PubMed]
Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature. 460: 278-282, 2009.
[CrossRef]
[PubMed]
Garrett CR, Eng C. Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther. 11: 937-949, 2011.
[CrossRef]
[PubMed]
Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB 3rd; Eastern Cooperative Oncology Group
Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer:
results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 25: 1539-1544, 2007.
[CrossRef]
[PubMed]
Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 135: 1079-1099, 2008.
[CrossRef]
[PubMed]
Grossmann AH, Samowitz WS. Epidermal growth factor receptor pathway mutations and colorectal cancer therapy. Arch Pathol Lab Med. 135: 1278-1282,
2011.
[CrossRef]
[PubMed]
Han DP, Zhu QL, Cui JT, Wang PX, Qu S, Cao QF, Zong YP, Feng B, Zheng MH, Lu AG. Polo-like kinase 1 is overexpressed in colorectal cancer and
participates in the migration and invasion of colorectal cancer cells. Med Sci Monit. 18: BR237-246, 2012.
[PubMed]
Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW. Genome-scale
analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 22: 271-282, 2012.
[CrossRef]
[PubMed]
Hsieh P, Yamane K. DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev. 129: 391-407, 2008.
[CrossRef]
[PubMed]
Hughes LA, Khalid-de Bakker CA, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator
phenotype in colorectal cancer: progress and problems. Biochim Biophys Acta. 1825: 77-85, 2012.
[PubMed]
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G et al.
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350: 2335-2342, 2004.
[CrossRef]
[PubMed]
Chan AO, Issa JP, Morris JS, Hamilton SR, Rashid A. Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol. 160: 529-536, 2002.
[CrossRef]
Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Raf kinase family. Cell Signal. 15: 463-469, 2003.
[CrossRef]
Iacopetta B, Kawakami K, Watanabe T. Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island
methylator phenotype the 5-fluorouracil-responsive subgroup? Int J Clin Oncol. 13: 498-503, 2008.
[CrossRef]
[PubMed]
Iacopetta B, Grieu F, Amanuel B. Microsatellite instability in colorectal cancer. Asia Pac J Clin Oncol. 6: 260-269, 2010.
[CrossRef]
[PubMed]
Ismaili N. Treatment of colorectal liver metastases. World J Surg Oncol. 9: 154, 2011.
[CrossRef]
[PubMed]
Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 4: 988-993, 2004.
[CrossRef]
[PubMed]
Jo WS, Carethers JM. Chemotherapeutic implications in microsatellite unstable colorectal cancer. Cancer Biomark. 2: 51-60, 2006.
[PubMed]
Jover R, Nguyen TP, Perez-Carbonell L, Zapater P, Paya A, Alenda C, Rojas E, Cubiella J, Balaguer F, Morillas JD, Clofent J, Bujanda L et al.
5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology.
140: 1174-1181, 2011.
[CrossRef]
[PubMed]
Jun SH, Kim TG, Ban C. DNA mismatch repair system. Classical and fresh roles. FEBS J. 273: 1609-1619, 2006.
[CrossRef]
[PubMed]
Kang GH. Four molecular subtypes of colorectal cancer and their precursor lesions. Arch Pathol Lab Med. 135: 698-703, 2011.
[PubMed]
Kim JH, Shin SH, Kwon HJ, Cho NY, Kang GH. Prognostic implications of CpG island hypermethylator phenotype in colorectal cancers. Virchows Arch. 455:
485-494, 2009.
[CrossRef]
[PubMed]
Kirby BJ, Jodari M, Loftus MS, Gakhar G, Pratt ED, Chanel-Vos C, Gleghorn JP, Santana SM, Liu H, Smith JP, Navarro VN, Tagawa ST et al. Functional
characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One. 7: e35976, 2012.
[CrossRef]
[PubMed]
Kisiel JB, Yab TC, Taylor WR, Chari ST, Petersen GM, Mahoney DW, Ahlquist DA. Stool DNA testing for the detection of pancreatic cancer: assessment of
methylation marker candidates. Cancer. 118: 2623-2631, 2012.
[CrossRef]
[PubMed]
Klaassen CH, Jeunink MA, Prinsen CF, Ruers TJ, Tan AC, Strobbe LJ, Thunnissen FB. Quantification of human DNA in feces as a diagnostic test for the
presence of colorectal cancer. Clin Chem. 49: 1185-1187, 2003.
[CrossRef]
[PubMed]
Kohne CH, Hofheinz R, Mineur L, Letocha H, Greil R, Thaler J, Fernebro E, Gamelin E, Decosta L, Karthaus M. First-line panitumumab plus
irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 138: 65-72, 2012.
[CrossRef]
[PubMed]
Kosinski L, Habr-Gama A, Ludwig K, Perez R. Shifting concepts in rectal cancer management: a review of contemporary primary rectal cancer treatment
strategies. CA Cancer J Clin. 62: 173-202, 2012.
[CrossRef]
[PubMed]
Kunkel TA, Erie DA. DNA mismatch repair. Annu Rev Biochem. 74: 681-710, 2005.
[CrossRef]
[PubMed]
Lassmann S, Danciu M, Muller M, Weis R, Makowiec F, Schulte-Monting J, Hopt UT, Werner M. Aurora A is differentially expressed and regulated in
chromosomal and microsatellite instable sporadic colorectal cancers. Mod Pathol. 22: 1385-1397, 2009.
[CrossRef]
[PubMed]
Lee S, Cho NY, Choi M, Yoo EJ, Kim JH, Kang GH. Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its
adverse prognosis in relation to KRAS/BRAF mutation. Pathol Int. 58: 104-113, 2008.
[CrossRef]
[PubMed]
Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 396: 643-649, 1998.
[CrossRef]
[PubMed]
Li BS, Wang XY, Xu AG, Ma FL, Ma QY, Li Z, Liu JH, Gan AH, Yu ZJ, Zhang XH, Jiang B. High-Resolution Melting Assay (HRMA) is a Simple and Sensitive
Stool-Based DNA Test for the Detection of Mutations in Colorectal Neoplasms. Clin Colorectal Cancer. 11: 280-290, 2012.
[CrossRef]
[PubMed]
Liang JT, Huang KC, Lai HS, Lee PH, Cheng YM, Hsu HC, Cheng AL, Hsu CH, Yeh KH, Wang SM, Tang C, Chang KJ. High-frequency microsatellite instability
predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative
bowel resection. Int J Cancer. 101: 519-525, 2002.
[CrossRef]
[PubMed]
Liao X, Morikawa T, Lochhead P, Imamura Y, Kuchiba A, Yamauchi M, Nosho K, Qian ZR, Nishihara R, Meyerhardt JA, Fuchs CS, Ogino S. Prognostic role of
PIK3CA mutation in colorectal cancer: cohort study and literature review. Clin Cancer Res. 18: 2257-2268, 2012.
[CrossRef]
[PubMed]
Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Cote JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P. KRAS
mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 66: 3992-3995, 2006.
[CrossRef]
[PubMed]
Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F et al. KRAS mutations as an
independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 26: 374-379, 2008.
[CrossRef]
[PubMed]
Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K et al. KRAS
codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J
Cancer. 101: 715-721, 2009.
[CrossRef]
[PubMed]
Lurje G, Lenz HJ. EGFR signaling and drug discovery. Oncology. 77: 400-410, 2009.
[CrossRef]
[PubMed]
Magbanua MJ, Sosa EV, Scott JH, Simko J, Collins C, Pinkel D, Ryan CJ, Park JW. Isolation and genomic analysis of circulating tumor cells from
castration resistant metastatic prostate cancer. BMC Cancer. 12: 78, 2012.
[CrossRef]
[PubMed]
Malesci A, Laghi L, Bianchi P, Delconte G, Randolph A, Torri V, Carnaghi C, Doci R, Rosati R, Montorsi M, Roncalli M, Gennari L et al. Reduced
likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res. 13: 3831-3839, 2007.
[CrossRef]
[PubMed]
Mao C, Yang ZY, Hu XF, Chen Q, Tang JL. PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS
wild-type metastatic colorectal cancer: a systematic review and meta-analysis. Ann Oncol. 23: 1518-1525, 2012.
[CrossRef]
[PubMed]
Markman B, Javier Ramos F, Capdevila J, Tabernero J. EGFR and KRAS in colorectal cancer. Adv Clin Chem. 51: 71-119, 2010.
[CrossRef]
Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 361: 2449-2460, 2009.
[CrossRef]
[PubMed]
Mejia A, Schulz S, Hyslop T, Weinberg DS, Waldman SA. Molecular staging individualizing cancer management. J Surg Oncol. 105: 468-474, 2012.
[CrossRef]
[PubMed]
Mikulova V, Kolostova K, Zima T. Methods for detection of circulating tumour cells and their clinical value in cancer patients. Folia Biol (Praha).
57: 151-161, 2011.
[PubMed]
Miller S, Steele S. Novel molecular screening approaches in colorectal cancer. J Surg Oncol. 105: 459-467, 2012.
[CrossRef]
[PubMed]
Min BH, Bae JM, Lee EJ, Yu HS, Kim YH, Chang DK, Kim HC, Park CK, Lee SH, Kim KM, Kang GH. The CpG island methylator phenotype may confer a survival
benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy. BMC Cancer. 11: 344, 2011.
[CrossRef]
[PubMed]
Modrich P. Mechanisms in eukaryotic mismatch repair. J Biol Chem. 281: 30305-30309, 2006.
[CrossRef]
[PubMed]
Mulsow J, Merkel S, Agaimy A, Hohenberger W. Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases. Br J Surg. 98:
1785-1791, 2011.
[CrossRef]
[PubMed]
Munzone E, Botteri E, Sandri MT, Esposito A, Adamoli L, Zorzino L, Sciandivasci A, Cassatella MC, Rotmensz N, Aurilio G, Curigliano G, Goldhirsch A et
al. Prognostic value of circulating tumor cells according to immunohistochemically defined molecular subtypes in advanced breast cancer. Clin Breast
Cancer. 12: 340-346, 2012.
[CrossRef]
[PubMed]
Murnane JP. Telomeres and chromosome instability. DNA Repair (Amst). 5: 1082-1092, 2006.
[CrossRef]
[PubMed]
Murnane JP. Telomere dysfunction and chromosome instability. Mutat Res. 730: 28-36, 2012.
[CrossRef]
[PubMed]
Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, Eshleman JR. Comparison of the microsatellite instability analysis system and the Bethesda
panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 8: 305-311, 2006.
[CrossRef]
[PubMed]
Nautiyal J, Du J, Yu Y, Kanwar SS, Levi E, Majumdar AP. EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic
carcinogen dimethylhydrazine. Am J Physiol Gastrointest Liver Physiol. 302: G655-663, 2012.
[CrossRef]
[PubMed]
Ng K, Zhu AX. Targeting the epidermal growth factor receptor in metastatic colorectal cancer. Crit Rev Oncol Hematol. 65: 8-20, 2008.
[CrossRef]
[PubMed]
Ogino S, Goel A. Molecular classification and correlates in colorectal cancer. J Mol Diagn. 10: 13-27, 2008.
[CrossRef]
[PubMed]
Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a
large population-based sample. J Mol Diagn. 9: 305-314, 2007.
[CrossRef]
[PubMed]
O’Hagan RC, Chang S, Maser RS, Mohan R, Artandi SE, Chin L, DePinho RA. Telomere dysfunction provokes regional amplification and deletion in cancer
genomes. Cancer Cell. 2: 149-155, 2002.
[CrossRef]
Okamoto I. Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy. FEBS J. 277: 309-315, 2010.
[CrossRef]
[PubMed]
Pai RK, Jayachandran P, Koong AC, Chang DT, Kwok S, Ma L, Arber DA, Balise RR, Tubbs RR, Shadrach B, Pai RK. BRAF-mutated, microsatellite-stable
adenocarcinoma of the proximal colon: an aggressive adenocarcinoma with poor survival, mucinous differentiation, and adverse morphologic features. Am
J Surg Pathol. 36: 744-752, 2012.
[CrossRef]
[PubMed]
Pantel K, Alix-Panabieres C. Detection methods of circulating tumor cells. J Thorac Dis. 4: 446-447, 2012.
[PubMed]
Perea J, Lomas M, Hidalgo M. Molecular basis of colorrectal cancer: towards an individualized management? Rev Esp Enferm Dig. 103: 29-35, 2011.
[CrossRef]
[PubMed]
Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, Frattini M, Riva C, Andreola S, Bajetta E, Bertario L, Leo E et al. PI3KCA/PTEN
deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol. 20: 84-90, 2009.
[CrossRef]
[PubMed]
Phelps RA, Broadbent TJ, Stafforini DM, Jones DA. New perspectives on APC control of cell fate and proliferation in colorectal cancer. Cell Cycle. 8:
2549-2556, 2009.
[CrossRef]
[PubMed]
Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 138: 2059-2072, 2010.
[CrossRef]
[PubMed]
Pino MS, Chung DC. Microsatellite instability in the management of colorectal cancer. Expert Rev Gastroenterol Hepatol. 5: 385-399, 2011.
[CrossRef]
[PubMed]
Popat S, Houlston RS. A systematic review and meta-analysis of the relationship between chromosome 18q genotype, DCC status and colorectal cancer
prognosis. Eur J Cancer. 41: 2060-2070, 2005.
[CrossRef]
[PubMed]
Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, Lambrechts D, Van Cutsem E, Tejpar S. PIK3CA mutations are not a major determinant
of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res. 15: 3184-3188, 2009.
[CrossRef]
[PubMed]
Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, Diener MK, Buchler MW, Koch M, Weitz J. Meta-analysis shows that detection of
circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 138: 1714-1726, 2010.
[CrossRef]
[PubMed]
Reik W, Lewis A. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet. 6: 403-410, 2005.
[CrossRef]
[PubMed]
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B et al. Prognostic
role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J
Clin Oncol. 28: 466-474, 2010.
[CrossRef]
[PubMed]
Sakaizawa K, Goto Y, Kiniwa Y, Uchiyama A, Harada K, Shimada S, Saida T, Ferrone S, Takata M, Uhara H, Okuyama R. Mutation analysis of BRAF and KIT in
circulating melanoma cells at the single cell level. Br J Cancer. 106: 939-946, 2012.
[CrossRef]
[PubMed]
Samowitz WS, Albertsen H, Herrick J, Levin TR, Sweeney C, Murtaugh MA, Wolff RK, Slattery ML. Evaluation of a large, population-based sample supports
a CpG island methylator phenotype in colon cancer. Gastroenterology. 129: 837-845, 2005a.
[CrossRef]
[PubMed]
Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, Wolff RK, Slattery ML. Poor survival associated with the BRAF V600E mutation in
microsatellite-stable colon cancers. Cancer Res. 65: 6063-6069, 2005b.
[CrossRef]
[PubMed]
Samuels Y, Waldman T. Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol. 347: 21-41, 2010.
[CrossRef]
[PubMed]
Samuels Y, Diaz LA, Jr., Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE.
Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 7: 561-573, 2005.
[CrossRef]
[PubMed]
Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, French AJ, Kabat B, Foster NR, Torri V, Ribic C, Grothey A et al. Defective
mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 28: 3219-3226,
2010.
[CrossRef]
[PubMed]
Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P, De Dosso S, Mazzucchelli L, Frattini M,
Siena S, Bardelli A. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res.
69: 1851-1857, 2009.
[CrossRef]
[PubMed]
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build
crypt-villus structures in vitro without a mesenchymal niche. Nature. 459: 262-265, 2009.
[CrossRef]
[PubMed]
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H. Paneth cells constitute the
niche for Lgr5 stem cells in intestinal crypts. Nature. 469: 415-418, 2011.
[CrossRef]
[PubMed]
Sawai H, Yasuda A, Ochi N, Ma J, Matsuo Y, Wakasugi T, Takahashi H, Funahashi H, Sato M, Takeyama H. Loss of PTEN expression is associated with
colorectal cancer liver metastasis and poor patient survival. BMC Gastroenterol. 8: 56, 2008.
[CrossRef]
[PubMed]
Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc
Natl Acad Sci USA. 103: 1412-1417, 2006.
[CrossRef]
[PubMed]
Schofield L, Watson N, Grieu F, Li WQ, Zeps N, Harvey J, Stewart C, Abdo M, Goldblatt J, Iacopetta B. Population-based detection of Lynch syndrome in
young colorectal cancer patients using microsatellite instability as the initial test. Int J Cancer. 124: 1097-1102, 2009.
[CrossRef]
[PubMed]
Schuebel KE, Chen W, Cope L, Glockner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH et al.
Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet. 3: 1709-1723, 2007.
[CrossRef]
[PubMed]
Shen L, Toyota M, Kondo Y, Lin E, Zhang L, Guo Y, Hernandez NS, Chen X, Ahmed S, Konishi K, Hamilton SR, Issa JP. Integrated genetic and epigenetic
analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA. 104: 18654-18659, 2007.
[CrossRef]
[PubMed]
Sinicrope FA, Rego RL, Halling KC, Foster N, Sargent DJ, La Plant B, French AJ, Laurie JA, Goldberg RM, Thibodeau SN, Witzig TE. Prognostic impact of
microsatellite instability and DNA ploidy in human colon carcinoma patients. Gastroenterology. 131: 729-737, 2006.
[CrossRef]
[PubMed]
Sleijfer S, Gratama JW, Sieuwerts AM, Kraan J, Martens JW, Foekens JA. Circulating tumour cell detection on its way to routine diagnostic
implementation? Eur J Cancer. 43: 2645-2650, 2007.
[CrossRef]
[PubMed]
Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, Rajdev L, Mariadason JM, Tanaka K, Goel S. PTEN gene expression and mutations in
the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic
colorectal cancer. Clin Colorectal Cancer. 11: 143-150, 2012.
[CrossRef]
[PubMed]
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. Microsatellite instability in colorectal cancer. Br J Surg. 93: 395-406, 2006.
[CrossRef]
[PubMed]
Spano JP, Fagard R, Soria JC, Rixe O, Khayat D, Milano G. Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and
therapeutic perspectives. Ann Oncol. 16: 189-194, 2005.
[CrossRef]
[PubMed]
Sun YF, Yang XR, Zhou J, Qiu SJ, Fan J, Xu Y. Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance. J
Cancer Res Clin Oncol. 137: 1151-1173, 2011.
[CrossRef]
[PubMed]
Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, Seruca R, Iacopetta B, Hamelin R. Evaluation of tumor microsatellite instability using
five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 123: 1804-1811, 2002.
[CrossRef]
[PubMed]
Takeuchi K, Ito F. Receptor tyrosine kinases and targeted cancer therapeutics. Biol Pharm Bull. 34: 1774-1780, 2011.
[CrossRef]
[PubMed]
Tejpar S, Van Cutsem E. Molecular and genetic defects in colorectal tumorigenesis. Best Pract Res Clin Gastroenterol. 16: 171-185, 2002.
[CrossRef]
[PubMed]
Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E. Association of KRAS G13D Tumor Mutations With Outcome in Patients With
Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab. J Clin Oncol. 30: 3570-3577, 2012.
[CrossRef]
[PubMed]
Thorsteinsson M, Soletormos G, Jess P. Low number of detectable circulating tumor cells in non-metastatic colon cancer. Anticancer Res. 31: 613-617,
2011.
[PubMed]
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 96:
8681-8686, 1999.
[CrossRef]
[PubMed]
Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G et al. Cetuximab and
chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 360: 1408-1417, 2009.
[CrossRef]
[PubMed]
Vecchione L, Jacobs B, Normanno N, Ciardiello F, Tejpar S. EGFR-targeted therapy. Exp Cell Res. 317: 2765-2771, 2011.
[CrossRef]
[PubMed]
Vidaurreta M, Sanchez-Munoz R, Veganzones S, Rafael S, Gutierrez M, de-la-Orden V, Fernandez C, Arroyo M, Cerdan FJ, Maestro de las Casas ML. Vascular
endothelial growth factor gene polymorphisms in patients with colorectal cancer. Rev Esp Enferm Dig. 102: 20-31, 2010.
[CrossRef]
[PubMed]
Vilar E, Scaltriti M, Balmana J, Saura C, Guzman M, Arribas J, Baselga J, Tabernero J. Microsatellite instability due to hMLH1 deficiency is
associated with increased cytotoxicity to irinotecan in human colorectal cancer cell lines. Br J Cancer. 99: 1607-1612, 2008.
[CrossRef]
[PubMed]
Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2: 489-501, 2002.
[CrossRef]
[PubMed]
Walther A, Houlston R, Tomlinson I. Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut. 57: 941-950,
2008.
[CrossRef]
[PubMed]
Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I, Kerr D. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 9:
489-499, 2009.
[CrossRef]
[PubMed]
Wang Z, Cummins JM, Shen D, Cahill DP, Jallepalli PV, Wang TL, Parsons DW, Traverso G, Awad M, Silliman N, Ptak J, Szabo S et al. Three classes of
genes mutated in colorectal cancers with chromosomal instability. Cancer Res. 64: 2998-3001, 2004.
[CrossRef]
[PubMed]
Warren CM, Landgraf R. Signaling through ERBB receptors: multiple layers of diversity and control. Cell Signal. 18: 923-933, 2006.
[CrossRef]
[PubMed]
Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L et al. CpG island
methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 38:
787-793, 2006.
[CrossRef]
[PubMed]
White BD, Chien AJ, Dawson DW. Dysregulation of Wnt/beta-catenin signaling in gastrointestinal cancers. Gastroenterology. 142: 219-232, 2012.
[CrossRef]
[PubMed]
Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S et al. The genomic landscapes of
human breast and colorectal cancers. Science. 318: 1108-1113, 2007.
[CrossRef]
[PubMed]
Wu M, Rivkin A, Pham T. Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal
cancer. Clin Ther. 30: 14-30, 2008.
[CrossRef]
[PubMed]
Xu N, Wang SQ, Tan D, Gao Y, Lin G, Xi R. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol.
354: 31-43, 2011.
[CrossRef]
[PubMed]
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2: 127-137, 2001.
[CrossRef]
[PubMed]
Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, Kondo C, Mizota A, Utsunomiya S, Muro K, Yatabe Y. BRAF mutation is a powerful prognostic
factor in advanced and recurrent colorectal cancer. Br J Cancer. 104: 856-862, 2011.
[CrossRef]
[PubMed]
Zlobec I, Bihl M, Foerster A, Rufle A, Lugli A. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal
cancers based on protein marker expression and molecular features. J Pathol. 225: 336-343, 2011.
[CrossRef]
[PubMed]
Zou H, Taylor WR, Harrington JJ, Hussain FT, Cao X, Loprinzi CL, Levine TR, Rex DK, Ahnen D, Knigge KL, Lance P, Jiang X, Smith DI, Ahlquist DA. High
detection rates of colorectal neoplasia by stool DNA testing with a novel digital melt curve assay. Gastroenterology. 136: 459-470, 2009.
[CrossRef]
[PubMed]
Zuckerman V, Wolyniec K, Sionov RV, Haupt S, Haupt Y. Tumour suppression by p53: the importance of apoptosis and cellular senescence. J Pathol. 219:
3-15, 2009.
[PubMed]
|
CITED
0
|
