Absence of PPP2R1B gene alterations in primary ovarian cancers

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.