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Khirurgii

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Year 2016 Vol. 24 No 2

REVIEWS

D.M. PASEVICH, S.A. SUSHKOU, V.M. SEMENOV

MOLECULAR GENETIC ASPECTS OF MALIGNANT COLON TUMORS

EE "Vitebsk State Medical University"
The Republic of Belarus

Today colorectal cancer is widely considered to be one of the world leaders in cancer incidence. There are many Colorectal Cancer Screening Programs for the detection of colorectal cancer; however, the identification of this disease in the late stages remains high. It points the disadvantages of the existing methods and seems to testify to a need of the new methods creation for early detection of cancer. This review presents the current literature on the role of genetic factors in colorectal cancer pathogenesis at the molecular level. The characteristics, localization and functions of some genes such as APC, MLH, MSH, PMS, KRAS, NRAS, BRAF, P53, BIRC5, involved in the occurrence of benign tumors of the colon, and then the conversion of normal cells into cancerous cells are presented. The information about the clinical and prognostic value, idetification of treatment effectiveness in choosing the types of chemotherapy drugs is given. Molecular and genetic techniques applied to identify these genes are described. The role of molecular genetics in the early diagnosis of malignancy of benign tumors is defined. The genetic factors, causing genetic predisposition (familial adenomatous polyposis, Lynch syndrome) are described as well as mutations in genes resulting in the appearance of non-inherited forms of colorectal cancer.

Keywords: Colorectal Cancer Screening Programs, colorectal cancer, molecular genetic diagnosis, familial adenomatous polyposis, Lynch syndrome, survivin, genetic factor
p. 184-192 of the original issue
References
  1. Zemlianoi VP, Trofimova TN, Nepomniashchaia SL, Dement'eva TV. Sovremennye metody diagnostiki i otsenki rasprostranennosti raka obodochnoi i priamoi kishki [Modern methods of diagnosis and evaluation of the prevalence of colorectal cancer]. Prakt Onkologiia. 2005;6(2):71-81.
  2. Kokhniuk VT. Kolorektal'nyi rak [Colorectal cancer]. Minsk, RB: Kharvest; 2005. 384 p.
  3. Sukonko OG, Krasnyi SA. Algoritmy diagnostiki i lecheniia zlokachestvennykh novoobrazovanii [Algorithms for the diagnosis and treatment of malignant neoplasms]. Minsk, RB; 2012. 584 p.
  4. Starinskii VV, Petrova GV, Chissov VI. Zabolevaemost' naseleniia Rossii zlokachestvennymi novoobrazovaniiami v 2000 g [Incidence of the population of malignant neoplasms in Russia in 2000]. Ros Onkol Zhurn. 2002;(3):39-44.
  5. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology. 1993 May;104(5):1535-49.
  6. Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027-38.
  7. Iwamoto M, Ahnen DJ, Franklin WA, Maltzman TH. Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues. Carcinogenesis. 2000 Nov;21(11):1935-40.
  8. Fultz KE, Gerner EW. APC-dependent regulation of ornithine decarboxylase in human colon tumor cells. Mol Carcinog. 2002 May;34(1):10-8.
  9. Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol. 2003 Mar;5(3):211-15.
  10. Bunyan DJ, Shea-Simonds J, Reck AC, Finnis D, Eccles DM. Genotype-phenotype correlations of new causative APC gene mutations in patients with familial adenomatous polyposis. J Med Genet. 1995 Sep; 32(9): 728–731.
  11. Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T, et al. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet. 1995 Mar;4(3):337-40.
  12. Morin PJ, Vogelstein B, Kinzler KW. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7950-4.
  13. Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet. 1999 Nov;36(11):801-18.
  14. Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ. Hereditary factors in cancer. Study of two large midwestern kindreds. Arch Intern Med. 1966 Feb;117(2):206-12.
  15. Rahner N, Steinke V, Schlegelberger B, Eisinger F, Hutter P, Olschwang S. Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM). - update 2012. Eur J Hum Genet. 2013 Jan;21(1). doi: 10.1038/ejhg.2012.164.
  16. Baglioni S, Genuardi M. Simple and complex genetics of colorectal cancer susceptibility. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129C(1):35-43.
  17. Baranova AV, Iankovskii NK. Geny-supressory opukholevogo rosta. Molekuliar Biologiia [A tumor suppressor gene]. 1998;32(2):206-18.
  18. Herman JG. Hypermethylation of tumor suppressor genes in cancer. Semin Cancer Biol. 1999 Oct;9(5):359-67.
  19. Liubchenko LN. Kliniko-genotipicheskie varianty semeinogo raka tolstoi kishki [Clinical and genetic variants of the family colon cancer]. Prakt Onkologiia. 2005;6(2):132-36.
  20. Watson P, Lynch HT. The tumor spectrum in HNPCC. Anticancer Res. 1994 Jul-Aug;14(4B):1635-39.
  21. Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W. Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J. 2005 Dec 1;392(Pt 2):249-61.
  22. Imianitov EN. Standartnye i potentsial'nye markery pri opukholiakh zheludochno-kishechnogo trakta [Standard and potential markers of tumors of the gastrointestinal tract]. Prakt Onkologiia. 2012;13(4):219-28.
  23. Vinogradov AV, Rezaikin AV, Sergeev AG. Detektsiia tochechnykh mutatsii genov KRAS I NRAS pri ostrykh mieloidnykh leikozakh s ispol'zovaniem tekhnologii priamogo avtomaticheskogo sekvenirovaniia [Detection of point mutations in the genes KRAS and KRAS in acute myeloid leukemia using the technology of direct automatic sequencing]. Vestn Bashkir Un-ta. 2014;19(3):845-47.
  24. Cerottini JP, Caplin S, Saraga E, Givel JC, Benhattar J. The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg. 1998 Mar;175(3):198-202.
  25. Vladimirova LY, Kit OI, Nikipelova EA. Abramova NA. Resilts of monoclonal antibodies against EGFR-receptors application in patients with metastatic colorectal cancer (mCRC). J Clin Oncol. 2013;31(suppl; abstr e14701). – P.800.
  26. Imianitov EN. Vyiavlenie mutatsii v gene BRAF dlia vybora terapii melanomy [Identification of mutations in the BRAF gene for melanoma therapy choice]. Arkh Patologii. 2012;74(5):65-71.
  27. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. doi: 10.1200/JCO.2010.33.5091.
  28. Chumakov PM. Belok r53 i ego universal'nye funktsii v mnogokletochnom organizme [The protein p53 and its universal function in a multicellular organism]. Uspekhi Biol Khimii. 2007;47(1):3-52.
  29. Laptenko O, Prives C. Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ. 2006 Jun;13(6):951-61.
  30. Horn HF, Vousden KH. Coping with stress: multiple ways to activate p53. Oncogene. 2007; 26:1306–16. doi:10.1038/sj.onc.1210263.
  31. David-Pfeuty T, Nouvian-Dooghe Y, Sirri V, Roussel P, Hernandez-Verdun D. Common and reversible regulation of wild-type p53 function and of ribosomal biogenesis by protein kinases in human cells. Oncogene. 2001 Sep 20;20(42):5951-63.
  32. Hamroun D, Kato S, Ishioka C, Claustres M, Béroud C, Soussi T. The UMD TP53 database and website: update and revisions. Hum Mutat. 2006 Jan;27(1):14-20.
  33. Pugacheva EN, Ivanov AV, Kravchenko JE, Kopnin BP, Levine AJ, Chumakov PM. Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil. Oncogene. 2002 Jul 11;21(30):4595-600.
  34. Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005 Dec;17(6):631-36.
  35. Pavlidou A, Dalamaga M, Kroupis C, Konstantoudakis G, Belimezi M, Athanasas G, et al. Survivin isoforms and clinicopathological characteristics in colorectal adenocarcinomas using real-time qPCR. World J Gastroenterol. 2011 Mar 28;17(12):1614-21. doi: 10.3748/wjg.v17.i12.1614.
  36. Ge QX, Li YY, Nie YQ, Zuo WG, Du YL. Expression of survivin and its four splice variants in colorectal cancer and its clinical significances. Med Oncol. 2013 Jun;30(2):535. doi: 10.1007/s12032-013-0535-6.
  37. Li F. Survivin study: what is the next wave? J Cell Physiol. 2003 Oct;197(1):8-29.
  38. Li F. Role of survivin and its splice variants in tumorigenesis. Br J Cancer. 2005 Jan 31;92(2):212-16.
  39. Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I, et al. HBXIP functions as a cofactor of survivin in apoptosis suppression. EMBO J. 2003 Jun 2;22(11):2729-40.
  40. Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006 Oct;7(10):988-94.
  41. Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008 Jan;8:61-70 . doi: 10.1038/nrc2293.
  42. Altieri DC. The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr Opin Cell Biol. 2006 Dec;18(6):609-15.
  43. Lens SM, Vader G, Medema RH. The case for Survivin as mitotic regulator. Curr Opin Cell Biol. 2006 Dec;18(6):616-22.
  44. Harfouche R, Hasséssian HM, Guo Y, Faivre V, Srikant CB, Yancopoulos GD, et al. Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells. Microvasc Res. 2002 Jul;64(1):135-47.
  45. Nees M, Geoghegan JM, Munson P, Prabhu V, Liu Y, Androphy E, et al. Human papillomavirus type 16 E6 and E7 proteins inhibit differentiation-dependent expression of transforming growth factor-beta2 in cervical keratinocytes. Cancer Res. 2000 Aug 1;60(15):4289-98.
  46. Zhao H, Granberg F, Elfineh L, Pettersson U, Svensson C. Strategic attack on host cell gene expression during adenovirus infection. J Virol. 2003 Oct;77(20):11006-15.
  47. Punga T, Akusjärvi G. Adenovirus 2 E1B-55K protein relieves p53-mediated transcriptional repression of the survivin and MAP4 promoters. FEBS Lett. 2003 Sep 25;552(2-3):214-18.
  48. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998 Nov 15;58(22):5071-74.
  49. Kawasaki H, Toyoda M, Shinohara H, Okuda J, Watanabe I, Yamamoto T, et al. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer. 2001 Jun 1;91(11):2026-32.
  50. Lin LJ, Zheng CQ, Jin Y, Ma Y, Jiang WG, Ma T. Expression of survivin protein in human colorectal carcinogenesis. World J Gastroenterol. 2003 May;9(5):974-77.
  51. Kim PJ, Plescia J, Clevers H, Fearon ER, Altieri DC. Survivin and molecular pathogenesis of colorectal cancer. Lancet. 2003 Jul 19;362(9379):205-9.
  52. Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, et al. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res. 2001 Dec 15;61(24):8664-67.
  53. Zhang T, Fields JZ, Ehrlich SM, Boman BM. The chemopreventive agent sulindac attenuates expression of the antiapoptotic protein survivin in colorectal carcinoma cells. J Pharmacol Exp Ther. 2004 Feb;308(2):434-37.
Address for correspondence:
210023, the Republic of Belarus,
Vitebsk, pr. Frunze, 27,
Vitebskiy gosudarstvennyiy meditsinskiy universitet,
kafedra obschey khirurgii,
e-mail: pasevich-dmitry@mail.ru,
Pasevich Dmitriy Mihaylovich
Information about the authors:
Pasevich D.M. An assistant of the general surgery chair of EE "Vitebsk State Medical University".
Sushkou S.A. PhD, an associate professor, Vice-Rector (Science) of EE "Vitebsk State Medical University".
Semenov V.M. MD, professor, a head of the infectious diseases chair of EE "Vitebsk State Medical University".
Contacts | ©Vitebsk State Medical University, 2007-2023