Skip to main content
SpringerLink
Log in

Molecular Pathology of Colon and Small Bowel Cancers: Sporadic Type

  • Chapter
  • First Online:
Molecular Pathology of Neoplastic Gastrointestinal Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 7))

  • 1451 Accesses

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third most common cause of cancer death in men and women in the USA and accounts for 9 % of all new cancer cases and of all cancer deaths. In contrast, the incidence of small bowel cancer is low and accounts for 0.4 % of all new cases and 0.2 % of all cancer deaths. It is currently believed that most sporadic colorectal cancers arise from preexisting precursor lesions, including adenoma, dysplasia and recently serrated polyps, but a small percentage of colorectal cancers can arise de novo without identifiable precursor lesions. The majority of colorectal cancers develop through an “adenoma–carcinoma sequence” beginning from transformation of normal colorectal epithelium to an adenomatous intermediate and then to adenocarcinoma. The molecular pathogenesis of colorectal cancer including genetic and epigenetic alterations has been extensively studied in the past two decades and is among one the best understood among human neoplasms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jemal A, Siegel R, Xu J, et al. Cancer Statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Morson B. President’s address: the polyp-cancer sequence in the large bowel. Proc R Soc Med. 1974;67:451–457.

    PubMed  CAS  Google Scholar 

  3. Fearon E, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–767.

    Article  PubMed  CAS  Google Scholar 

  4. Toyota M, Ho C, Ahuja N, et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res. 1999;59:2307–2312.

    PubMed  CAS  Google Scholar 

  5. Toyota M, Ohe-Toyota M, Ahuja N, et al. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci USA. 2000;97:710–715.

    Article  PubMed  CAS  Google Scholar 

  6. Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG Island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999;96:8681–8686.

    Article  PubMed  CAS  Google Scholar 

  7. Ionov Y, Peinado MA, Malkhosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–561.

    Article  PubMed  CAS  Google Scholar 

  8. Thibodeau SN, Berg G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–819.

    Article  PubMed  CAS  Google Scholar 

  9. Peltomaki P, Lothe RA, Aaltonen LA, et al. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal cancer syndrome. Cancer Res. 1993;53:5853–5855.

    PubMed  CAS  Google Scholar 

  10. Wood LD, Parsons DW, Jones S, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318:1108–1113.

    Article  PubMed  CAS  Google Scholar 

  11. Leary R, Lin J, Cummins J, et al. Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proc Natl Acad Sci USA. 2008;105:16226–16229.

    Article  Google Scholar 

  12. Powell S, Zilz N, Beazer-Barclay Y, et al. APC mutations occur early during colorectal tumoriogenesis. Nature. 1992;359:235–237.

    Article  PubMed  CAS  Google Scholar 

  13. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159–170.

    Article  PubMed  CAS  Google Scholar 

  14. Benhattar J, Losi L, Chaubert P, et al. Prognostic significance of K-ras mutations in colorectal carcinoma. Gastroenterology. 1993;104:1044–1048.

    PubMed  CAS  Google Scholar 

  15. Moerkerk P, Arends JW, van Driel M, et al. Type and number of Ki-ras point mutations relate to stage of human colorectal cancer. Cancer Res. 1994;54:3376–3378.

    PubMed  CAS  Google Scholar 

  16. Santini D, Loupakis F, Vincenzi B, et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008;13:1270–1275.

    Article  PubMed  CAS  Google Scholar 

  17. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse tumor types. Nature. 1989;342:705–708.

    Article  PubMed  CAS  Google Scholar 

  18. Baker SJ, Preisinger AC, Jessup JM, et al. p53 gene mutations occur in combination with 17p allelic deletions as late event in colorectal tumorigenesis. Cancer Res. 1990;50:7717–7722.

    PubMed  CAS  Google Scholar 

  19. Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990;247:49–56.

    Article  PubMed  CAS  Google Scholar 

  20. Thiagalingam S, Lengauer C, Leach FS, et al. Evaluation of candidate tumor suppressor genes on chromosome 18 in colorectal cancers. Nat Genet. 1996;13:343–346.

    Article  PubMed  CAS  Google Scholar 

  21. Bacolod MD, Barany F. Gene dysregulation driven by somatic copy number aberrations-biological and clinical implications in colon tumors: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diag. 2010;12:552–561.

    Article  CAS  Google Scholar 

  22. Cottrell S, Bicknell D, Kaklamanis L, et al. Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet. 1992;340:626–630.

    Article  PubMed  CAS  Google Scholar 

  23. Miyaki M, Konishi M, Kikuchi-Yanoshita R, et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994;54:3011–3020.

    PubMed  CAS  Google Scholar 

  24. Miyoshi Y, Nagase H, Ando H, et al. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1992;1:229–233.

    Article  PubMed  CAS  Google Scholar 

  25. Otori K, Konishi M, Sugiyama K, et al. Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue. Cancer. 1998;83:896–900.

    Article  PubMed  CAS  Google Scholar 

  26. Esteller M, Sparks A, Toyota M, et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 2000;60:4366–4371.

    PubMed  CAS  Google Scholar 

  27. Rubinfeld B, Albert I, Porfiri E, et al. Binding of GSK3b to the APC-b-catenin complex and regulation of complex assembly. Science. 1996;272:1023–1026.

    Article  PubMed  CAS  Google Scholar 

  28. Mann B, Gelos M, Siedow A, et al. Target genes of beta-catenin-T-cell-factor/lymphoid-enhancer-factor signaling in human ­colorectal carcinomas. Proc Natl Acad Sci USA. 1999;96: 1603–1608.

    Article  PubMed  CAS  Google Scholar 

  29. Sparks A, Morin P, Vogelstein B, et al. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 1998;58:1130–1134.

    PubMed  CAS  Google Scholar 

  30. Shimizu Y, Ikeda S, Fujimori M, et al. Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability. Genes Chromosomes Cancer. 2002;3:73–81.

    Article  CAS  Google Scholar 

  31. Leslie A, Carey F, Pratt N, et al. The colorectal adenoma-carcinoma sequence. Br J Surg. 2002;89:845–860.

    Article  PubMed  CAS  Google Scholar 

  32. Vogelstein B, Lane D, Levine A. Surfing the p53 network. Nature. 2000;408:307–310.

    Article  PubMed  CAS  Google Scholar 

  33. Levine A. p53, the cellular gatekeeper for growth and division. Cell. 1997;88:323–331.

    Article  PubMed  CAS  Google Scholar 

  34. Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009;9:724–737.

    Article  PubMed  CAS  Google Scholar 

  35. Beroud C, Soussi T. The UMD-p53 database: new mutations and analysis tools. Hum Mutat. 2003;21:176–181.

    Article  PubMed  CAS  Google Scholar 

  36. Cho K, Oliner J, Simons J, et al. The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics. 1994;19: 525–531.

    Article  PubMed  CAS  Google Scholar 

  37. Takagi Y, Kohmura H, Futamura M, et al. Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. Gastroenterology. 1996;111:1369–1372.

    Article  PubMed  CAS  Google Scholar 

  38. Takagi Y, Koumura H, Futamura M, et al. Somatic alterations of the SMAD-2 gene in human colorectal cancers. Br J Cancer. 1995;78:1152–1155.

    Article  Google Scholar 

  39. Wu C, Kirley S, Xiao H, et al. Cables enhances cdk2 tyrosine 152 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers. Cancer Res. 2001;61:7325–7332.

    PubMed  CAS  Google Scholar 

  40. Park do Y, Sakamoto H, Kirley S, et al. The Cables gene on chromosomes 18q is silences by promoter hypermethylation and allelic loss in human colorectal cancer. Am J Pathol. 2007;171:1509–1519.

    Article  PubMed  CAS  Google Scholar 

  41. Chan TL, Zhao W, Leung SY, et al. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res. 2003;63:4878–4881.

    PubMed  CAS  Google Scholar 

  42. Samuels Y, Wang Z, Bardelli A, et al. High frequency if mutations of the PIK3CA gene in human cancers. Science. 2004;304:554.

    Article  PubMed  CAS  Google Scholar 

  43. Samuels Y, Velculescu VE. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle. 2004;3:1221–1224.

    Article  PubMed  CAS  Google Scholar 

  44. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science. 2001;293:1068–1070.

    Article  PubMed  CAS  Google Scholar 

  45. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21.

    Article  PubMed  CAS  Google Scholar 

  46. Baylin SB, Herman JG, Graff JR, et al. Alterations in DNA methylation—A fundamental aspect of neoplasia. Adv Cancer Res. 1998;72:141–196.

    Article  PubMed  CAS  Google Scholar 

  47. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301:89–92.

    Article  PubMed  CAS  Google Scholar 

  48. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet. 1999;21:163–167.

    Article  PubMed  CAS  Google Scholar 

  49. Kane MF, Loda M, Gaida GM, et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997;57:808–811.

    PubMed  CAS  Google Scholar 

  50. Merlo A, Herman JG, Mao L, et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995;1:686–692.

    Article  PubMed  CAS  Google Scholar 

  51. Ahuja N, Li Q, Mohan AL, et al. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 1998;58:5489–5494.

    PubMed  CAS  Google Scholar 

  52. Issa JP, Ottaviano YL, Celano P, et al. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994;7:536–540.

    Article  PubMed  CAS  Google Scholar 

  53. Suzuki H, Gabrielson E, Chen W, et al. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet. 2002;31:141–149.

    Article  PubMed  CAS  Google Scholar 

  54. Costello JF, Fruhwald MC, Smiraglia DJ, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000;24:132–138.

    Article  PubMed  CAS  Google Scholar 

  55. Toyota M, Shen L, Ohe-Toyota M, et al. Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors. Cancer Res. 2000;60:4044–4048.

    PubMed  CAS  Google Scholar 

  56. Devereux TR, Horikawa I, Anna CH, et al. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res. 1999;59:6087–6090.

    PubMed  CAS  Google Scholar 

  57. Ahuja N, Mohan AL, Li Q, et al. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res. 1997;57:3370–3374.

    PubMed  CAS  Google Scholar 

  58. Hawkins N, Norrie M, Cheong K, et al. CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability. Gastroenterology. 2002;122:1376–1387.

    Article  PubMed  CAS  Google Scholar 

  59. Whitehall VL, Wynter CV, Walsh MD, et al. Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer. Cancer Res. 2002;62:6011–6014.

    PubMed  CAS  Google Scholar 

  60. Koinuma K, Shitoh K, Miyakura Y, et al. Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas. Int J Cancer. 2004;108:237–242.

    Article  PubMed  CAS  Google Scholar 

  61. Wang L, Cunningham JM, Winters JL, et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003;63:5209–5212.

    PubMed  CAS  Google Scholar 

  62. Esteller M, Toyota M, Sanchez-Cespedes M, et al. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. Cancer Res. 2000;60:2368–2371.

    PubMed  CAS  Google Scholar 

  63. Rashid A, Shen L, Morris JS, et al. CpG island methylation in colorectal adenomas. Am J Pathol. 2001;159:1129–1135.

    Article  PubMed  CAS  Google Scholar 

  64. Chan AO, Broaddus RR, Houlihan PS, et al. CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol. 2002;160:1823–1830.

    Article  PubMed  CAS  Google Scholar 

  65. Li H, Myeroff L, Smiraglia D, et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci USA. 2003;100:8412–8417.

    Article  PubMed  CAS  Google Scholar 

  66. Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110:748–755.

    Article  PubMed  CAS  Google Scholar 

  67. Rashid A, Houlihan PS, Booker S, et al. Phenotypic and molecular characteristics of hyperplastic polyposis. Gastroenterology. 2000;119:323–332.

    Article  PubMed  CAS  Google Scholar 

  68. Jeevaratnam P, Cottier DS, Browett PJ, et al. Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome. J Pathol. 1996;179:20–25.

    Article  PubMed  CAS  Google Scholar 

  69. Park SJ, Rashid A, Lee JH, et al. Frequent CpG island methylation in serrated adenomas of the colorectum. Am J Pathol. 2003;162:815–822.

    Article  PubMed  CAS  Google Scholar 

  70. Chan AO, Issa JP, Morris JS, et al. Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol. 2002;160:529–536.

    Article  PubMed  CAS  Google Scholar 

  71. Jass JR. Serrated route to colorectal cancer: back street or super highway? J Pathol. 2001;193:283–285.

    Article  PubMed  CAS  Google Scholar 

  72. Hawkins NJ, Bariol C, Ward RL. The serrated neoplasia pathway. Pathology. 2002;34:548–555.

    PubMed  CAS  Google Scholar 

  73. Hawkins NJ, Ward RL. Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst. 2001;93:1307–1313.

    Article  PubMed  CAS  Google Scholar 

  74. Bronner CE, Baker SM, Morrison PT, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368:258–261.

    Article  PubMed  CAS  Google Scholar 

  75. Papadopoulos N, Nicolaides NC, Wei YF, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263:1625–1629.

    Article  PubMed  CAS  Google Scholar 

  76. Leach FS, Nicolaides NC, Papadopoulos N, et al. Mutation of a Muts D homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993;75:1215–1225.

    Article  PubMed  CAS  Google Scholar 

  77. Fishel R, Lescoe MK, Rao MR, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75:1027–1038 [Erratum, Cell 1994;77:167].

    Article  PubMed  CAS  Google Scholar 

  78. Miyaki M, Konishi M, Tanaka K, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997;17:271–272.

    Article  PubMed  CAS  Google Scholar 

  79. Koldner RD, Tytell JD, Schmeits JL, et al. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999;59:5068–5074.

    Google Scholar 

  80. Nicolaides NC, Papadopoulos N, Liu B, et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994;371:75–80.

    Article  PubMed  CAS  Google Scholar 

  81. Herman JG, Umar A, Polyak K, et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA. 1998;95:6870–6875.

    Article  PubMed  CAS  Google Scholar 

  82. Veigel ML, Kasturi L, Olechnowicz J, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing MSI cancers. Proc Natl Acad Sci USA. 1998;95:8698–8702.

    Article  Google Scholar 

  83. Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite instability for cancer detection and familial predisposition: development of international criteria for the detection of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–5275.

    PubMed  CAS  Google Scholar 

  84. Malkhosyan SR, Yamamoto H, Piao Z, et al. Late onset and high incidence of colon cancer of the mutator phenotype with hypermethylated hMLH1 gene in women. Gastroenterology. 2000; 119:598.

    Article  PubMed  CAS  Google Scholar 

  85. Wright CM, Dent OF, Barker M, et al. The prognostic significance of extensive microsatellite instability in sporadic clinicopathologic stage C colorectal cancer. Br J Surg. 2000;87:1197–1202.

    Article  PubMed  CAS  Google Scholar 

  86. Alexander J, Watanabe T, Wu TT, et al. Histopathologic identification of colon cancer with microsatellite instability. Am J Pathol. 2001;98:527–735.

    Article  Google Scholar 

  87. Kim H, Jen J, Vogelstein B, et al. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994;145:148–156.

    PubMed  CAS  Google Scholar 

  88. Rüschoff J, Dietmaier W, Lüttges J, et al. Poorly differentiated colonic adenocarcinoma, medullary type: clinical, phenotypic, and molecular characteristics. Am J Pathol. 1997;150: 1815–1825.

    PubMed  Google Scholar 

  89. Fujiwara T, Stolker JM, Watanabe T, et al. Accumulated clonal genetic alterations in familial and sporadic colorectal carcinomas with widespread instability in microsatellite sequences. Am J Pathol. 1998;153:1063–1078.

    Article  PubMed  CAS  Google Scholar 

  90. Samowitz WS, Holden JA, Curtin K, et al. Inverse relationship between microsatellite instability and K-ras and p53 gene alteration in colon cancer. Am J Pathol. 2001;158:1517–1524.

    Article  PubMed  CAS  Google Scholar 

  91. Mirabelli-Primdahl L, Gryfe R, Kim H, et al. Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res. 1999;59:3346–3351.

    PubMed  CAS  Google Scholar 

  92. Deng G, Bell I, Crawley S, et al. BRAF mutation is frequently present in sporadic cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 2004;10:191–195.

    Article  PubMed  CAS  Google Scholar 

  93. Markowitz S, Wang J, Myeroff L, et al. Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science. 1995;268:1336–1338.

    Article  PubMed  CAS  Google Scholar 

  94. Souza RF, Appel R, Yin J, et al. The insulin-like growth factor II receptor gene is a target of microsatellite instability in human gastrointestinal tumors. Nat Genet. 1996;14:255–257.

    Article  PubMed  CAS  Google Scholar 

  95. Yamamoto H, Sawai H, Weber TK, et al. Somatic frameshift mutations in hereditary nonpolyposis colorectal cancer. Cancer Res. 1998;58:997–1003.

    PubMed  CAS  Google Scholar 

  96. Parsons R, Myeroff L, Liu B, et al. Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res. 1995;55:5548–5550.

    PubMed  CAS  Google Scholar 

  97. Jen J, Kim H, Piantadosi S, et al. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med. 1994;331:213–221.

    Article  PubMed  CAS  Google Scholar 

  98. Watanabe T, Wu T-T, Catalano PJ, et al. Molecular predictors of survival after chemotherapy for colon cancer. N Engl J Med. 2001;344:1196–1206.

    Article  PubMed  CAS  Google Scholar 

  99. Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77.

    Article  PubMed  CAS  Google Scholar 

  100. Shen L, Catalano PJ, Benson AB III, et al. Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil based chemotherapy. Clin Cancer Res. 2007;13:6093–6098.

    Article  PubMed  CAS  Google Scholar 

  101. Samowitz WS, Albertsen H, Herrick J, et al. Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology. 2005;129:837–845.

    Article  PubMed  CAS  Google Scholar 

  102. Jover R, Nguyen T-P, Perez-Carbonell L, et al. 5-Fluorouracil adjuvant chemotherapy does not increase survival with CpG adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology. 2011;140:1174–1181.

    Article  PubMed  CAS  Google Scholar 

  103. Rubic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–257.

    Article  Google Scholar 

  104. Liévre A, Bachet JB, Le Corre D, et al. KRAS mutation is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–3995.

    Article  PubMed  Google Scholar 

  105. Liévre A, Bachet JB, Boige V, et al. KRAS mutation as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374–379.

    Article  PubMed  CAS  Google Scholar 

  106. Jhawer M, Goel S, Wilson AJ, et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res. 2008;68:1953–1961 [Erratum, Cancer Res 2008;68:6859.].

    Article  PubMed  CAS  Google Scholar 

  107. Laurent-Puig P, Cayre A, Manceau G, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27:5924–5930.

    Article  PubMed  CAS  Google Scholar 

  108. van Cutsem E, Köhne C-H, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Eng J Med. 2009;360:1408–1417.

    Article  Google Scholar 

  109. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, AND PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–762.

    Article  PubMed  CAS  Google Scholar 

  110. Warth A, Kloor M, Schirmacher P, et al. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol. 2011;24:564–570.

    Article  PubMed  CAS  Google Scholar 

  111. Diosdado B, Buffart TE, Watkins R, et al. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin Cancer Res. 2010;16:1391–1401.

    Article  PubMed  CAS  Google Scholar 

  112. Blaker H, von Herbay A, Penzel R, et al. Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene. Oncogene. 2002;21:158–164.

    Article  PubMed  CAS  Google Scholar 

  113. Berkhout M, Nagtegaal ID, Cornelissen SJ, et al. Chromosomal and methylation alterations in sporadic and familial adenomatous polyposis-related duodenal carcinomas. Mod Pathol. 2007;20: 1253–1262.

    Article  PubMed  CAS  Google Scholar 

  114. Rashid A, Hamilton SR. Genetic alterations in sporadic and Crohn’s-associated adenocarcinomas of the small intestine. Gastroenterology. 1997;113:127–135.

    Article  PubMed  CAS  Google Scholar 

  115. Wheeler JM, Warren BF, Mortensen NJ, et al. An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut. 2002;50:218–223.

    Article  PubMed  CAS  Google Scholar 

  116. Arai M, Shimizu S, Imai Y, et al. Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small intestine. Int J Cancer. 1997;70:390–395.

    Article  PubMed  CAS  Google Scholar 

  117. Zhang MQ, Chen ZM, Wang HL. Immunohistochemical investigation of tumorigenic pathways in small intestinal adenocarcinoma: a comparison with colorectal adenocarcinoma. Mod Pathol. 2006;19:573–580.

    Article  PubMed  CAS  Google Scholar 

  118. Younes N, Fulton N, Tanaka R, et al. The presence of K-12 ras mutations in duodenal adenocarcinomas and the absence of ras mutations in other small bowel adenocarcinomas and carcinoid tumors. Cancer. 1997;79:1804–1808.

    Article  PubMed  CAS  Google Scholar 

  119. Muneyuki T, Watanabe M, Yamanaka M, et al. Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas. Dig Dis Sci. 2000;45:2022–2028.

    Article  PubMed  CAS  Google Scholar 

  120. Schonleben F, Qiu W, Allendorf JD, et al. Molecular analysis of PIK3CA, BRAF, and RAS oncogenes in periampullary and ampullary adenomas and carcinomas. J Gastrointest Surg. 2009;13:1510–1516.

    Article  PubMed  Google Scholar 

  121. Kim SG, Chan AOO, Wu TT, et al. Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas. Gastroenterology. 2003;124:1300–1310.

    Article  PubMed  Google Scholar 

  122. Overman MJ, Pozadzides J, Kopetz S, et al. Immunophenotype and molecular characterization of adenocarcinoma of the small intestine. Br J Cancer. 2010;102:144–150.

    Article  PubMed  CAS  Google Scholar 

  123. Lynch HT, Lynch JF, Lynch PM, et al. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer. 2008;7:27–39.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe, Houston, TX, USA

    Asif Rashid M.D., Ph.D.

Authors
  1. Asif Rashid M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asif Rashid M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Pathology & Cell Biology, Columbia University, New York, 10032, New York, USA

    Antonia R. Sepulveda

  2. Division of Gastroenterology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    John P. Lynch

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rashid, A. (2013). Molecular Pathology of Colon and Small Bowel Cancers: Sporadic Type. In: Sepulveda, A., Lynch, J. (eds) Molecular Pathology of Neoplastic Gastrointestinal Diseases. Molecular Pathology Library, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-6015-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6015-2_8

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4614-6014-5

  • Online ISBN: 978-1-4614-6015-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation