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Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the FHIT gene: Evaluation of allelic imbalance at FHIT, RB1 and TP53 in relation to survival
Author(s) -
Helland Åslaug,
Kraggerud Sigrid Marie,
Kristensen Gunnar B.,
Holm Rut,
Abeler Vera M.,
Huebner Kay,
BørresenDale AnneLise,
Lothe Ragnhild A.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001015)88:2<217::aid-ijc11>3.0.co;2-i
Subject(s) - fhit , biology , loss of heterozygosity , chromosome , gene , chromosome 17 (human) , allele , locus (genetics) , tumor suppressor gene , genetics , microbiology and biotechnology , cancer research , carcinogenesis
Chromosome arm 3p is re‐arranged in many tumor types, including cervical carcinomas. Putative tumor‐suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci ( p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse‐free survival was associated with AI in the TP53 gene in both a univariate ( p = 0.0003) and a multivariate ( p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis. Int. J. Cancer 88:217–222, 2000. © 2000 Wiley‐Liss, Inc.