title: PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes.
abstract: Somatic mutations in PPP2R1A, which encodes a scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have recently been described in different types of gynecological neoplasias. To extend this observation, we examined the frequency of PPP2R1A mutation in some major histological subtypes of type I and type II ovarian carcinoma. Mutational analysis of PPP2R1A (exons 5 and 6) was performed on 88 primary ovarian carcinomas, including mucinous, clear cell, high-grade serous, and high-grade endometrioid ovarian carcinoma. In addition, exons 9 and 20 of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and exon 15 of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) were sequenced and compared across the different histological subtypes. Finally, survival analysis was performed to determine any prognostic significance of these mutations. Mutations in PPP2R1A were rare: detected in 4.5% (1/22) of clear cell, 4.5% (1/22) of high-grade serous, and 6.7% (1/15) of high-grade endometrioid ovarian carcinoma. Interestingly, no PPP2R1A mutations were observed in mucinous ovarian carcinoma. A higher frequency of PIK3CA mutations (50%, 11/22) was found in clear cell carcinoma and a higher frequency of KRAS mutations (24.1%, 7/29) was observed in mucinous carcinoma. In addition, high-grade endometrioid ovarian carcinoma exhibited KRAS and PIK3CA mutations in 26.7% (4/15) and 20% (3/15) of cases, respectively. Survival analysis showed no significant association between mutational status and overall survival of patients. This study indicates that the PPP2R1A mutation occurs at a lower frequency compared to other gynecological malignancies, irrespective of the histological subtype.
authors.affiliation: Shimane University School of Medicine, Enyacho 89-1, Izumo, Shimane, 6938501, Japan. kn88@med.shimane-u.ac.jp
authors.forename: Munmun
authors.initials: M
authors.lastname: Rahman
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Mohammed Tanjimur
authors.initials: MT
authors.lastname: Rahman
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katagiri
authors.forename: Atsuko
authors.initials: A
authors.lastname: Katagiri
authors.forename: Tomoka
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Masako
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Iida
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Otsuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakayama
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; C517191:PPP2R1A protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D054648:Protein Phosphatase 2; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins