Genetic-based biomarkers and next-generation sequencing: the future of personalized care in colorectal cancer.

The past 5 years have witnessed extraordinary advances in the field of DNA sequencing technology. What once took years to accomplish with Sanger sequencing can now be accomplished in a matter of days with next-generation sequencing (NGS) technology. This has allowed researchers to sequence individual genomes and match combinations of mutations with specific diseases. As cancer is inherently a disease of the genome, it is not surprising to see NGS technology already being applied to cancer research with promises of greater understanding of carcinogenesis. While the task of deciphering the cancer genomic code remains ongoing, we are already beginning to see the application of genetic-based testing in the area of colorectal cancer. In this article we will provide an overview of current colorectal cancer genetic-based biomarkers, namely mutations and other genetic alterations in cancer genome DNA, discuss recent advances in NGS technology and speculate on future directions for the application of NGS technology to colorectal cancer diagnosis and treatment.

[1]  S. Gruber,et al.  Microsatellite instability in colorectal cancer—the stable evidence , 2010, Nature Reviews Clinical Oncology.

[2]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[3]  Dongsheng Tu,et al.  K-ras mutations and benefit from cetuximab in advanced colorectal cancer. , 2008, The New England journal of medicine.

[4]  P. Vihko,et al.  Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers , 1999, British Journal of Cancer.

[5]  Sabine Tejpar,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. , 2010, The Lancet. Oncology.

[6]  W. Scheithauer,et al.  Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. , 2010, World journal of gastroenterology.

[7]  J. Baron,et al.  Colon and Rectum , 2002 .

[8]  S. Gabriel,et al.  Advances in understanding cancer genomes through second-generation sequencing , 2010, Nature Reviews Genetics.

[9]  Silvia Benvenuti,et al.  Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. , 2007, Cancer research.

[10]  B. Taillon,et al.  Second Generation Sequencing of the Mesothelioma Tumor Genome , 2010, PloS one.

[11]  A. Matakidou,et al.  Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  R. Rosell,et al.  Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in patients with resected colorectal cancer , 2001, Diseases of the colon and rectum.

[13]  A. Carrato,et al.  UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy , 2010, British Journal of Cancer.

[14]  B. Uzzan,et al.  Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. , 2009, European journal of cancer.

[15]  E. Van Cutsem,et al.  Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. , 2009, The New England journal of medicine.

[16]  M. Metzker Sequencing technologies — the next generation , 2010, Nature Reviews Genetics.

[17]  S Srivastava,et al.  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. , 1998, Cancer research.

[18]  J. Rothberg,et al.  Detection of oncogenic mutations in the EGFR gene in lung adenocarcinoma with differential sensitivity to EGFR tyrosine kinase inhibitors. , 2005, Cold Spring Harbor symposia on quantitative biology.

[19]  John D McPherson,et al.  Next-generation gap , 2009, Nature Methods.

[20]  J. Reid,et al.  Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  J. Lupski,et al.  The complete genome of an individual by massively parallel DNA sequencing , 2008, Nature.

[22]  M. Hawn,et al.  Prognostic significance of allelic lost at chromosome 18q21 for stage II colorectal cancer. , 1998, Gastroenterology.

[23]  A. Stanley,et al.  Value of predictive genetic testing in management of hereditary non‐polyposis colorectal cancer (HNPCC) , 2000, The Medical journal of Australia.

[24]  Elena Edelman,et al.  A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities , 2008, Proceedings of the National Academy of Sciences.

[25]  Daniel J. Freeman,et al.  Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Kenneth Offit,et al.  Genome-wide association studies of cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  R. Kandpal,et al.  The era of 'omics unlimited. , 2009, BioTechniques.

[28]  R. Labianca,et al.  Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  L. Mazzucchelli,et al.  Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  G. Milano,et al.  Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients. , 2010, British journal of clinical pharmacology.

[31]  Xiao-dong Zhu,et al.  Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: a meta-analysis of 22 studies. , 2010, European journal of cancer.

[32]  K. Calzone,et al.  Genetic testing for cancer susceptibility. , 2008, The Surgical clinics of North America.

[33]  D. Lane,et al.  P53 abnormalities and outcomes in colorectal cancer: a systematic review , 2005, British Journal of Cancer.

[34]  R. Houlston,et al.  Systematic review of microsatellite instability and colorectal cancer prognosis. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  E. Birney,et al.  A small cell lung cancer genome reports complex tobacco exposure signatures , 2009, Nature.

[36]  Nancy F. Hansen,et al.  Accurate Whole Human Genome Sequencing using Reversible Terminator Chemistry , 2008, Nature.

[37]  R. Gafà,et al.  Microsatellite Instability and Colorectal Cancer Prognosis , 2005, Clinical Cancer Research.

[38]  Y. Nakamura,et al.  Genetic alterations during colorectal-tumor development. , 1988, The New England journal of medicine.

[39]  L. Mazzucchelli,et al.  Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer , 2009, PloS one.

[40]  A. Jakobsen,et al.  Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  I. Winship,et al.  Controversies and ethical issues in cancer-genetics clinics. , 2005, The Lancet. Oncology.

[42]  J. Lau,et al.  MTHFR gene polymorphisms and response to chemotherapy in colorectal cancer: a meta-analysis. , 2009, Pharmacogenomics.

[43]  C. Bokemeyer,et al.  Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  Sabine Tejpar,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. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  M. Loriot,et al.  Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  P. Peltomäki Role of DNA mismatch repair defects in the pathogenesis of human cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  E. Van Cutsem,et al.  Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  K. Kinzler,et al.  Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status , 2002, Nature.

[49]  Amy E. Hawkins,et al.  DNA sequencing of a cytogenetically normal acute myeloid leukemia genome , 2008, Nature.

[50]  Zhaohui S. Qin,et al.  An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. , 2010, Cancer cell.

[51]  J. Maguire,et al.  Integrative analysis of the melanoma transcriptome. , 2010, Genome research.

[52]  Daniel J Sargent,et al.  Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. , 2003, The New England journal of medicine.

[53]  J. Rogers The finished genome sequence of Homo sapiens. , 2003, Cold Spring Harbor symposia on quantitative biology.

[54]  K. Cohn,et al.  The significance of allelic deletions and aneuploidy in colorectal carcinoma , 1997, Cancer.

[55]  R. Gafà,et al.  Chromosome 18q allelic loss and prognosis in stage II and III colon cancer , 1998, International journal of cancer.

[56]  Ken Chen,et al.  Recurring mutations found by sequencing an acute myeloid leukemia genome. , 2009, The New England journal of medicine.

[57]  Deni Elliott,et al.  Genetic Information Nondiscrimination Act , 2008 .

[58]  D. Sargent,et al.  Revised TN categorization for colon cancer based on national survival outcomes data. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[59]  C. Compton,et al.  Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  P J Catalano,et al.  Molecular predictors of survival after adjuvant chemotherapy for colon cancer. , 2001, The New England journal of medicine.

[61]  L. Becquemont,et al.  Pharmacogenomics of adverse drug reactions: practical applications and perspectives. , 2009, Pharmacogenomics.

[62]  D. Kerr,et al.  Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study , 2007, The Lancet.

[63]  A. Lièvre,et al.  Oncogenic mutations as predictive factors in colorectal cancer , 2010, Oncogene.

[64]  E. Fearon Molecular Genetics of Colorectal Cancer , 1995, Annals of the New York Academy of Sciences.

[65]  D. Chung,et al.  The cables gene on chromosome 18Q regulates colon cancer progression in vivo , 2005, Cancer biology & therapy.

[66]  Norman Wolmark,et al.  Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  Daniel F Hayes,et al.  ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  A. Lièvre,et al.  KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[69]  Adopted on March American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[70]  P. Johnston,et al.  5-Fluorouracil: mechanisms of action and clinical strategies , 2003, Nature Reviews Cancer.

[71]  N. Funel,et al.  PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  Paul Medvedev,et al.  Computational methods for discovering structural variation with next-generation sequencing , 2009, Nature Methods.

[73]  J. Marshall Risk assessment in Stage II colorectal cancer. , 2010, Oncology.

[74]  Peter R. Thom,et al.  Ethical and legal aspects of cancer genetic testing. , 2007, Seminars in oncology.

[75]  Linda Mol,et al.  Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. , 2009, The New England journal of medicine.

[76]  A. Norman,et al.  Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. , 1998, Journal of the National Cancer Institute.

[77]  W. Ansorge Next-generation DNA sequencing techniques. , 2009, New biotechnology.

[78]  Sangsoo Kim,et al.  The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group. , 2009, Genome research.

[79]  Muhammad Akhtar Ali,et al.  Molecular pathways in tumor progression: from discovery to functional understanding. , 2009, Molecular bioSystems.

[80]  R. Gray,et al.  Randomised trials of HIV prevention , 2007, The Lancet.

[81]  R. Aebersold,et al.  Applying mass spectrometry-based proteomics to genetics, genomics and network biology , 2009, Nature Reviews Genetics.

[82]  Richard Simon,et al.  Gene expression-based prognostic signatures in lung cancer: ready for clinical use? , 2010, Journal of the National Cancer Institute.