The PPP2R1B gene has recently been implicated as a tumor suppressor based o
n the finding of somatic alterations in lung and colon cancers. PPP2R1B is
located on chromosome 11q22-24 which coincides with the site of frequent lo
ss of heterozygosity (LOH) in ovarian cancer. We investigated if the PPP2R1
B gene was inactivated in ovarian cancer by single strand conformational po
lymorphism (SSCP) and heteroduplex (HD) analysis of 99% of the coding regio
n. LOH at the PPP2R1B locus was detected in 32% of the malignant tumors but
no somatic alterations were detected in any of 65 malignant, five borderli
ne or six benign tumors. A germline G>A transition (GGC>GAC) in codon 90 wa
s detected in 4/76 tumors. This alteration has previously been described as
a mutation but on further investigation we found that the frequency of thi
s variant among 167 ovarian cancers (4.2%) was not statistically significan
tly different from that observed in 247 noncancer random controls (2.4%). W
e conclude that the PPP2R1B gene is not involved in the pathogenesis of ova
rian cancer. The codon 90 Gly>Asp alteration may represent a non-pathologic
al polymorphism and consequently the mutation frequency reported in lung ca
ncers may have been overstated and the designation of PPP2R1B as a tumor su
ppressor gene should be regarded with caution.