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Biomarkers and molecular diagnosis of gastrointestinal and pancreatic neoplasms

Nature Reviews Gastroenterology & Hepatology volume 7, pages 620–628 (2010)Cite this article

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Abstract

Standard protocols for the diagnosis of neoplasms in the gastrointestinal tract are based on histopathologic analysis in combination with clinical information. With the completion of the Human Genome Project in 2003, our understanding of the contribution of genetics to human disease has increased exponentially. This knowledge is gradually being incorporated into clinical decision-making. However, the rate at which molecular biomarkers are validated for use in mainstream clinical applications has lagged far behind that of biomarker discovery. Nevertheless, a number of molecular biomarkers are available for use in the diagnosis and management of gastrointestinal tract neoplasms. This article reviews the most common molecular biomarkers currently available for neoplasms of the luminal gastrointestinal tract and pancreas. In neoplasms of the esophagus, for which no biomarkers are currently used in routine clinical practice, those that have shown the most promise in early clinical validation studies are discussed.

Key Points

  • Personalized medicine relates to the tailoring of medical treatment to the individual characteristics of each patient

  • Biomarkers can assist in diagnosis and prognosis of a neoplasm or disease, prediction of progression, or response to therapy

  • Examples of biomarkers include tissue and serum proteins and nucleic acids

  • Measurement or detection of biomarkers can be performed in multiple matrices, including peripheral blood, biopsy or surgical resection tissue, and body fluids

  • While biomarkers for esophageal neoplasia remain in the investigation phase, multiple biomarkers are currently in clinical use in patients with tumors in the stomach, pancreas and colon

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References

  1. Feero, W. G., Guttmacher, A. E. & Collins, F. S. Genomic medicine—an updated primer. N. Engl. J. Med. 362, 2001–2011 (2010).

    CAS  PubMed  Google Scholar 

  2. Jankowski, J. A. & Odze, R. D. Biomarkers in gastroenterology: between hope and hype comes histopathology. Am. J. Gastroenterol. 104, 1093–1096 (2009).

    CAS  PubMed  Google Scholar 

  3. Dietel, M. & Sers, C. Personalized medicine and development of targeted therapies: The upcoming challenge for diagnostic molecular pathology. A review. Virchows Arch. 448, 744–755 (2006).

    PubMed  Google Scholar 

  4. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69, 89–95 (2001).

  5. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  6. Colotta, F., Allavena, P., Sica, A., Garlanda, C. & Mantovani, A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30, 1073–1081 (2009).

    CAS  PubMed  Google Scholar 

  7. Eloubeidi, M. A., Mason, A. C., Desmond, R. A. & El Serag, H. B. Temporal trends (1973–1997) in survival of patients with esophageal adenocarcinoma in the United States: a glimmer of hope? Am. J. Gastroenterol. 98, 1627–1633 (2003).

    PubMed  Google Scholar 

  8. Brown, L. M., Devesa, S. S. & Chow, W. H. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J. Natl Cancer Inst. 100, 1184–1187 (2008).

    PubMed  PubMed Central  Google Scholar 

  9. Tachibana, M., Hirahara, N., Kinugasa, S. & Yoshimura, H. Clinicopathologic features of superficial esophageal cancer: results of consecutive 100 patients. Ann. Surg. Oncol. 15, 104–116 (2008).

    PubMed  Google Scholar 

  10. Pech, O. et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus. Gut 57, 1200–1206 (2008).

    CAS  PubMed  Google Scholar 

  11. Bird-Lieberman, E. L. & Fitzgerald, R. C. Early diagnosis of oesophageal cancer. Br. J. Cancer 101, 1–6 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Adams, L. et al. Promoter methylation in cytology specimens as an early detection marker for esophageal squamous dysplasia and early esophageal squamous cell carcinoma. Cancer Prev. Res. (Phila Pa) 1, 357–361 (2008).

    CAS  PubMed Central  Google Scholar 

  13. Spechler, S. J. Clinical practice. Barrett's Esophagus. N. Engl. J. Med. 346, 836–842 (2002).

    PubMed  Google Scholar 

  14. Dulai, G. S., Guha, S., Kahn, K. L., Gornbein, J. & Weinstein, W. M. Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review. Gastroenterology 122, 26–33 (2002).

    PubMed  Google Scholar 

  15. Montgomery, E. et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum. Pathol. 32, 368–378 (2001).

    CAS  PubMed  Google Scholar 

  16. Souza, R. F. et al. Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus. Am. J. Gastroenterol. 100, 551–559 (2005).

    CAS  PubMed  Google Scholar 

  17. Zhang, H. Y. et al. Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett's esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G470–G478 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Reid, B. J., Levine, D. S., Longton, G., Blount, P. L. & Rabinovitch, P. S. Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am. J. Gastroenterol. 95, 1669–1676 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Rabinovitch, P. S., Longton, G., Blount, P. L., Levine, D. S. & Reid, B. J. Predictors of progression in Barrett's esophagus III: baseline flow cytometric variables. Am. J. Gastroenterol. 96, 3071–3083 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Reid, B. J. et al. Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am. J. Gastroenterol. 96, 2839–2848 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang, Q., Yu, C., Zhang, X. & Goyal, R. K. Comparison of DNA histograms by standard flow cytometry and image cytometry on sections in Barrett's adenocarcinoma. BMC. Clin. Pathol. 8, 5 (2008).

    PubMed  PubMed Central  Google Scholar 

  22. Rygiel, A. M. et al. Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens. Genes Chromosomes Cancer 47, 396–404 (2008).

    CAS  PubMed  Google Scholar 

  23. Galipeau, P. C. et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med. 4, e67 (2007).

    PubMed  PubMed Central  Google Scholar 

  24. Schulmann, K. et al. Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk. Oncogene 24, 4138–4148 (2005).

    CAS  PubMed  Google Scholar 

  25. Tapia, C. et al. Close association between HER-2 amplification and overexpression in human tumors of non-breast origin. Mod. Pathol. 20, 192–198 (2007).

    CAS  PubMed  Google Scholar 

  26. Tanner, M. et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann. Oncol. 16, 273–278 (2005).

    CAS  PubMed  Google Scholar 

  27. Grabsch, H., Sivakumar, S., Gray, S., Gabbert, H. E. & Muller, W. HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value - conclusions from 924 cases of two independent series. Cell Oncol. 32, 57–65 (2010).

    PubMed  PubMed Central  Google Scholar 

  28. Van Cutsem, E. et al. Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J. Clin. Oncol. 27, 18S (2009).

    Google Scholar 

  29. Hofmann, M. et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52, 797–805 (2008).

    CAS  PubMed  Google Scholar 

  30. Ruschoff, J. et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. doi:10.1007/s00428-00010-0952-2 (2010).

  31. Kim, M. A. et al. Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum. Pathol. 38, 1386–1393 (2007).

    CAS  PubMed  Google Scholar 

  32. Correa, P., Piazuelo, M. B. & Wilson, K. T. Pathology of gastric intestinal metaplasia: clinical implications. Am. J. Gastroenterol. 105, 493–498 (2010).

    PubMed  PubMed Central  Google Scholar 

  33. Miki, K. & Urita, Y. Using serum pepsinogens wisely in a clinical practice. J. Dig. Dis. 8, 8–14 (2007).

    CAS  PubMed  Google Scholar 

  34. Watanabe, Y. et al. Helicobacter pylori infection and gastric cancer. A nested case-control study in a rural area of Japan. Dig. Dis. Sci. 42, 1383–1387 (1997).

    CAS  PubMed  Google Scholar 

  35. Oliveira, C., Seruca, R. & Carneiro, F. Hereditary gastric cancer. Best Pract. Res. Clin. Gastroenterol. 23, 147–157 (2009).

    CAS  PubMed  Google Scholar 

  36. Machado, J. C. et al. E-cadherin gene mutations provide a genetic basis for the phenotypic divergence of mixed gastric carcinomas. Lab. Invest. 79, 459–465 (1999).

    CAS  PubMed  Google Scholar 

  37. Becker, K. F. et al. Identification of eleven novel tumor-associated E-cadherin mutations. Mutations in brief no. 215. Online. Hum. Mutat. 13, 171 (1999).

    CAS  PubMed  Google Scholar 

  38. Oliveira, C. et al. Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum. Mutat. 19, 510–517 (2002).

    CAS  PubMed  Google Scholar 

  39. Brooks-Wilson, A. R. et al. Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J. Med. Genet. 41, 508–517 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Suriano, G. et al. Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin. Cancer Res. 11, 5401–5409 (2005).

    CAS  PubMed  Google Scholar 

  41. Sircar, K. et al. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am. J. Surg. Pathol. 23, 377–389 (1999).

    CAS  PubMed  Google Scholar 

  42. Hirota, S. et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279, 577–580 (1998).

    CAS  PubMed  Google Scholar 

  43. Heinrich, M. C. et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299, 708–710 (2003).

    CAS  PubMed  Google Scholar 

  44. Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472–480 (2002).

    CAS  PubMed  Google Scholar 

  45. Dematteo, R. P. et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373, 1097–1104 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Miettinen, M., Majidi, M. & Lasota, J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur. J. Cancer 38 (Suppl 5), S39–S51 (2002).

    PubMed  Google Scholar 

  47. West, R. B. et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am. J. Pathol. 165, 107–113 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Liegl, B., Hornick, J. L., Corless, C. L. & Fletcher, C. D. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am. J. Surg. Pathol. 33, 437–446 (2009).

    PubMed  Google Scholar 

  49. Heinrich, M. C. et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 21, 4342–4349 (2003).

    CAS  PubMed  Google Scholar 

  50. Debiec-Rychter, M. et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur. J. Cancer 42, 1093–1103 (2006).

    CAS  PubMed  Google Scholar 

  51. Wang, C. M. et al. Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors. J. Cancer Res. Clin. Oncol. 136, 1065–1071 (2010).

    CAS  PubMed  Google Scholar 

  52. Heng, D. Y. & Kollmannsberger, C. Sunitinib. Recent Results Cancer Res. 184, 71–82 (2010).

    CAS  PubMed  Google Scholar 

  53. Association for Molecular Pathology (AMP). AMP test directory [online], (2010).

  54. Hidalgo, M. Pancreatic cancer. N. Engl. J. Med. 362, 1605–1617 (2010).

    CAS  PubMed  Google Scholar 

  55. Berger, A. C. et al. Postresection CA 19–19 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J. Clin. Oncol. 26, 5918–5922 (2008).

    PubMed  PubMed Central  Google Scholar 

  56. Hess, V. et al. CA 19–19 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol. 9, 132–138 (2008).

    CAS  PubMed  Google Scholar 

  57. Ferrone, C. R. et al. Perioperative CA19–19 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J. Clin. Oncol. 24, 2897–2902 (2006).

    CAS  PubMed  Google Scholar 

  58. Ko, A. H. et al. Serum CA19–19 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer. Br. J. Cancer 93, 195–199 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Greer, J. B., Lynch, H. T. & Brand, R. E. Hereditary pancreatic cancer: a clinical perspective. Best Pract. Res. Clin. Gastroenterol. 23, 159–170 (2009).

    CAS  PubMed  Google Scholar 

  60. Khalid, A. & Brugge, W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am. J. Gastroenterol. 102, 2339–2349 (2007).

    PubMed  Google Scholar 

  61. Brugge, W. R., Lauwers, G. Y., Sahani, D., Fernandez-del Castillo, C. & Warshaw, A. L. Cystic neoplasms of the pancreas. N. Engl. J. Med. 351, 1218–1226 (2004).

    CAS  PubMed  Google Scholar 

  62. Khalid, A. Differentiating neoplastic from benign lesions of the pancreas: translational techniques. Clin. Gastroenterol. Hepatol. 7 (11 Suppl.), S55–S58 (2009).

    CAS  PubMed  Google Scholar 

  63. Pitman, M. B. et al. Pancreatic cysts: preoperative diagnosis and clinical management. Cancer Cytopathol. 118, 1–13 (2010).

    PubMed  Google Scholar 

  64. Tanaka, M. et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 6, 17–32 (2006).

    PubMed  Google Scholar 

  65. Khalid, A. et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest. Endosc. 69, 1095–1102 (2009).

    PubMed  Google Scholar 

  66. Shen, J., Brugge, W. R., Dimaio, C. J. & Pitman, M. B. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer Cytopathol. 117, 217–227 (2009).

    Google Scholar 

  67. Center, M. M., Jemal, A. & Ward, E. International trends in colorectal cancer incidence rates. Cancer Epidemiol. Biomarkers Prev. 18, 1688–1694 (2009).

    PubMed  Google Scholar 

  68. Jemal, A. et al. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009).

    PubMed  Google Scholar 

  69. Ahlquist, D. A. Molecular detection of colorectal neoplasia. Gastroenterology 138, 2127–2139 (2010).

    CAS  PubMed  Google Scholar 

  70. Ahlquist, D. A. et al. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann. Intern. Med. 149, 441–450, W81 (2008).

    PubMed  PubMed Central  Google Scholar 

  71. Levin, B. et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J. Clin. 58, 130–160 (2008) (2008).

    PubMed  Google Scholar 

  72. Rex, D. K. et al. American College of Gastroenterology guidelines for colorectal cancer screening. Am. J. Gastroenterol. 104, 739–750 (2009).

    PubMed  Google Scholar 

  73. Plesec, T. P. & Hunt, J. L. KRAS mutation testing in colorectal cancer. Adv. Anat. Pathol. 16, 196–203 (2009).

    CAS  PubMed  Google Scholar 

  74. Normanno, N. et al. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat. Rev. Clin. Oncol. 6, 519–527 (2009).

    CAS  PubMed  Google Scholar 

  75. Allegra, C. J. et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J. Clin. Oncol. 27, 2091–2096 (2009).

    PubMed  Google Scholar 

  76. Engstrom, P. F. & National Comprehensive Cancer Network. Systemic therapy for advanced or metastatic colorectal cancer: National Comprehensive Cancer Network guidelines for combining anti-vascular endothelial growth factor and anti-epidermal growth factor receptor monoclonal antibodies with chemotherapy. Pharmacotherapy 28, 18S–22S (2008).

    CAS  PubMed  Google Scholar 

  77. Monzon, F. A. et al. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch. Pathol. Lab. Med. 133, 1600–1606 (2009).

    CAS  PubMed  Google Scholar 

  78. Macrae, F., du Sart, D. & Nasioulas, S. Familial adenomatous polyposis. Best Pract. Res. Clin. Gastroenterol. 23, 197–207 (2009).

    CAS  PubMed  Google Scholar 

  79. Knudsen, A. L., Bisgaard, M. L. & Bulow, S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam. Cancer 2, 43–55 (2003).

    PubMed  Google Scholar 

  80. Giardiello, F. M., Brensinger, J. D. & Petersen, G. M. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 121, 198–213 (2001).

    CAS  PubMed  Google Scholar 

  81. Al-Tassan, N. et al. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat. Genet. 30, 227–232 (2002).

    CAS  PubMed  Google Scholar 

  82. Sieber, O. M. et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N. Engl. J. Med. 348, 791–799 (2003).

    PubMed  Google Scholar 

  83. Nielsen, M. et al. Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). J. Med. Genet. 42, e54 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Lynch, H. T. et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin. Genet. 76, 1–18 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Peltomaki, P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J. Clin. Oncol. 21, 1174–1179 (2003).

    CAS  PubMed  Google Scholar 

  86. Boland, C. R. 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. Cancer Res. 58, 5248–5257 (1998).

    CAS  PubMed  Google Scholar 

  87. Cunningham, J. M. et al. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am. J. Hum. Genet. 69, 780–790 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Wahlberg, S. S. et al. Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res. 62, 3485–3492 (2002).

    CAS  PubMed  Google Scholar 

  89. Ribic, C. M. et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N. Engl. J. Med. 349, 247–257 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Elsaleh, H. et al. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355, 1745–1750 (2000).

    CAS  PubMed  Google Scholar 

  91. Carethers, J. M. et al. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 126, 394–401 (2004).

    CAS  PubMed  Google Scholar 

  92. Benatti, P. et al. Microsatellite instability and colorectal cancer prognosis. Clin. Cancer Res. 11, 8332–8340 (2005).

    CAS  PubMed  Google Scholar 

  93. Jover, R. et al. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut 55, 848–855 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. de Vos tot Nederveen Cappel, W. H. et al. Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer. Int. J. Cancer 109, 468–471 (2004).

    CAS  PubMed  Google Scholar 

  95. National Center for Biotechnology Information. GeneTests [online] (2010).

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Acknowledgements

R. F. Souza acknowledges the support of the US Office of Medical Research, Department of Veterans Affairs. She is the holder of NIH grants R01-DK63621 and R01-CA134571.

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Authors and Affiliations

  1. Departments of Pathology and Laboratory Medicine, VA North Texas Health Care System & University of Texas Southwestern Medical Center, Dallas VA Medical Center, 4500 South Lancaster Road, Dallas, TX 75216, USA

    Shelby D. Melton

  2. Department of Medicine, VA North Texas Health Care System & University of Texas Southwestern Medical Center, Dallas VA Medical Center, 4500 South Lancaster Road, Dallas, TX 75216, USA

    Rhonda F. Souza

  3. Caris Research Institute, Caris Life Sciences, 6655 North MacArthur Boulevard, Irving, TX 75039, USA

    Robert M. Genta

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Melton, S., Genta, R. & Souza, R. Biomarkers and molecular diagnosis of gastrointestinal and pancreatic neoplasms. Nat Rev Gastroenterol Hepatol 7, 620–628 (2010). https://doi.org/10.1038/nrgastro.2010.153

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