Allelic imbalance and mutations of the PTEN gene in ovarian cancer

The PTEN/MMACI/TEPI tumor-suppressor gene, which maps to chromosome 10q23.3 , is mutated and homozygously deleted in a variety of human tumors, includi ng endometrioid-type ovarian tumors. We examined 33 primary ovarian cancers and 3 ovarian borderline tumors for allelic imbalance (AI) of the 10q23.3 region using 5 polymorphic markers, including an insertion/deletion-type po lymorphic marker identified in intron 4 of the PTEN gene. Al at one or more loci was detected in 12 of 31 (39%) informative ovarian cancers and none o f 3 ovarian borderline tumors. The commonly deleted region was mapped betwe en the D10S215 and D10S541 loci, including the PTEN locus. Moreover, the in cidence of Al at the PTEN locus (38%) was the highest among the 5 loci exam ined. Therefore, we searched for mutations in the entire coding region of t he PTEN gene by PCR-SSCP and sequencing analyses in these tumors and 7 ovar ian cancer cell lines. Mutations were detected in 3 of the 33 (9%) ovarian cancers: 2 cases with double mutations and I case with a mutation on I alle le accompanied by deletions on both alleles in the poly T tract preceding t he splice acceptor site in intron 7. An intragenic deletion was detected in I of the 7 (14%) ovarian cancer cell lines. PTEN mutations were detected n ot only in the endometrioid type but also in the serous and mucinous types of ovarian cancer. However, PTEN was not mutated in the 12 tumors that show ed Al of the PTEN locus. Our results suggest that the PTEN gene plays an im portant role in the development of a subset but diverse histological types of ovarian tumors. However, it is possible that another tumor-suppressor ge ne in the close vicinity of the PTEN gene is also inactivated by Al of the 10q23.3 region. (C) 2000 Wiley-Liss, Inc.