Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors

✍ Scribed by Mayi Y. Arcellana-Panlilio; R. Maarten Egeler; Eva Ujack; Anthony Magliocco; Gavin C.E. Stuart; Stephen M. Robbins; Max J. Coppes

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 159 KB
• Volume: 35
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.10108

✦ Synopsis

Abstract

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.