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Evidence of a role for the INK4 family of cyclin‐dependent kinase inhibitors in ovarian granulosa cell tumors
Author(s) -
ArcellanaPanlilio Mayi Y.,
Egeler R. Maarten,
Ujack Eva,
Magliocco Anthony,
Stuart Gavin C.E.,
Robbins Stephen M.,
Coppes Max J.
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10108
Subject(s) - biology , cyclin dependent kinase , cancer research , exon , loss of heterozygosity , cyclin d , dna methylation , cyclin dependent kinase 4 , tumor suppressor gene , gene , microbiology and biotechnology , gene expression , genetics , carcinogenesis , cell cycle , cyclin dependent kinase 2 , allele
Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5% of all ovarian cancers. The molecular pathogenesis of these tumors is not well understood. We tested the hypothesis that cyclin‐dependent kinase inhibitors, specifically the in hibitors of the cyclin‐dependent k inase 4 (INK4) family, are targets for altered gene expression in GCTs. The status of RB1, INK4A, INK4B, INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by reverse transcription–polymerase chain reaction of total RNA and exon‐specific sequencing of genomic DNA. Tumors showing loss of INK4A expression were assayed further by exon‐deletion analysis and methylation‐specific PCR. None of the juvenile tumors demonstrated altered expression, but 7/12 (58%) adult GCTs lacked expression of INK4A, INK4B, or both. In one of these cases, we noted a homozygous deletion of the INK4A locus, and in the remaining tumors we found hypermethylation of the promoter region, a mechanism that can lead to gene inactivation. These data support a role for the INK4 family of CDK inhibitors in the biology of GCTs. © 2002 Wiley‐Liss, Inc.