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.