title: Association of HPV with genetic and epigenetic alterations in colorectal adenocarcinoma from Indian population.
abstract: Several studies from developing countries have shown human papillomavirus to be associated with colorectal cancers, but the molecular characteristics of such cancers are poorly known. We studied the various genetic variations like microsatellite instability (MSI), oncogenic mutations and epigenetic deregulations like CpG island methylation in HPV associated and nonassociated colorectal cancer patients from Indian population. HPV DNA was detected by PCR using My09/My11 and Gp5+/Gp6+ consensus primers and typed using HPV16 and HPV18 specific primers. MSI was detected using BAT 25 and BAT 26 markers, and mutation of KRAS, TP53 and BRAF V600E were detected by direct sequencing. Methyl specific polymerase chain reaction (MSP) was used to determine promoter methylation of the classical CIMP panel markers (P16, hMLH1, MINT1, MINT2 and MINT31) and other tumour-related genes (DAPK, RASSF1, BRCA1 and GSTP1). HPV DNA was detected in 34/93 (36.5 %) colorectal tumour tissues, HPV 18 being the predominant high-risk type. MSI was detected in 7.5 % cases; KRAS codon 12, 13, BRAF V600E and TP53 mutations were detected in 36.5, 3.2 and 37.6 % of the cases, respectively. CIMP-high was observed in 44.08 % cases. HPV presence was not associated with age, stage or grade of tumours, MSI or mutations in KRAS, TP53 or BRAF genes. Higher methylation frequencies of all genes/loci under study except RASSF1, as well as significantly higher CIMP-high characteristics were observed in HPV positive tumours as compared to negative cases. HPV in association with genetic and epigenetic features might be a potent risk factor for colorectal cancer in Indian population.
authors: Molecular Medicine Laboratory, Department of Biotechnology, Assam University, Silchar, 788011, Assam, India.
authors: Ruhina S
authors: RS
authors: Laskar
authors: Fazlur R
authors: FR
authors: Talukdar
authors: Javed H
authors: JH
authors: Choudhury
authors: Seram Anil
authors: SA
authors: Singh
authors: Sharbadeb
authors: S
authors: Kundu
authors: Bishal
authors: B
authors: Dhar
authors: Rosy
authors: R
authors: Mondal
authors: Sankar Kumar
authors: SK
authors: Ghosh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
references: Oral Oncol. 2013 Apr;49(4):345-53
references: 23265943
references: Virology. 1989 Dec;173(2):767-71
references: 2556855
references: J Med Virol. 2005 Mar;75(3):435-9
references: 15648077
references: Colorectal Dis. 2005 Sep;7(5):492-5
references: 16108887
references: Nat Rev Cancer. 2004 Oct;4(10):769-80
references: 15510158
references: Carcinogenesis. 2012 Jul;33(7):1286-93
references: 22552403
references: Tumour Biol. 2011 Aug;32(4):653-9
references: 21625944
references: Genome Med. 2013 Feb 05;5(2):15
references: 23419152
references: Mol Cancer. 2013 Jan 03;12 :1
references: 23286373
references: Eur J Cancer Prev. 2013 May;22(3):277-85
references: 22990004
references: Cancer Causes Control. 2013 Jun;24(6):1207-22
references: 23563998
references: Oncogene. 1992 Aug;7(8):1541-7
references: 1321402
references: BMC Cancer. 2010 Mar 26;10:117
references: 20346145
references: Asian Pac J Cancer Prev. 2011;12(3):749-51
references: 21627377
references: Nat Rev Cancer. 2010 Aug;10(8):550-60
references: 20592731
references: CA Cancer J Clin. 2014 Mar-Apr;64(2):104-17
references: 24639052
references: Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2288-97
references: 21817125
references: Cancer Res. 2012 Apr 15;72(8):2036-44
references: 22367214
references: Mol Carcinog. 2014 Feb;53 Suppl 1:E181-6
references: 23168910
references: Nature. 2012 Jul 18;487(7407):330-7
references: 22810696
references: PLoS One. 2013 Apr 15;8(4):e60996
references: 23596512
references: Eur J Surg Oncol. 2007 Jun;33(5):569-74
references: 17321098
references: Mol Med Rep. 2012 Apr;5(4):1053-7
references: 22218684
references: J Pharm Biomed Anal. 2000 Aug 15;23(2-3):581-9
references: 10933552
references: J Gastroenterol Hepatol. 2012 Sep;27(9):1423-31
references: 22694276
references: Anal Biochem. 2009 Aug 1;391(1):77-9
references: 19442642
references: J Med Virol. 2009 Oct;81(10):1792-6
references: 19697401
references: PLoS One. 2013;8(4):e60142
references: 23573237
references: Colorectal Dis. 2013 Aug;15(8):e420-8
references: 23895733
references: Nat Rev Clin Oncol. 2010 Mar;7(3):153-62
references: 20142816
references: Gynecol Oncol. 2007 Jun;105(3):662-6
references: 17360030
references: J Clin Microbiol. 2005 Nov;43(11):5428-34
references: 16272465
references: J Virol. 2008 Sep;82(17):8820-7
references: 18579583
references: Nat Rev Gastroenterol Hepatol. 2011 Oct 18;8(12):686-700
references: 22009203
references: Indian J Med Res. 2014 Feb;139(2):314-8
references: 24718409
references: PLoS One. 2012;7(11):e50533
references: 23226306
references: Gastroenterol Hepatol Bed Bench. 2013 Summer;6(3):120-8
references: 24834258
references: Lancet. 1992 May 2;339(8801):1070-3
references: 1349102
references: J Clin Oncol. 1997 Mar;15(3):1008-12
references: 9060540
references: Cancer Sci. 2014 Apr;105(4):409-17
references: 24521534
references: Cancer Res. 2001 Jan 1;61(1):249-55
references: 11196170
references: Eur J Cancer. 2014 May;50(8):1446-61
references: 24560489
references: Cancer Causes Control. 2010 May;21(5):737-43
references: 20087645
references: CA Cancer J Clin. 2013 Jan;63(1):57-81
references: 23258613
references: Arch Pathol Lab Med. 2008 Oct;132(10 ):1657-65
references: 18834226
references: Gut. 1995 Jul;37(1):87-90
references: 7672688