TY - JOUR
T1 - Somatic mutations of PPP2R1A in ovarian and uterine carcinomas
AU - Shih, Ie Ming
AU - Panuganti, Pradeep K.
AU - Kuo, Kuan Tin
AU - Mao, Tsui Lien
AU - Kuhn, Elisabetta
AU - Jones, Sian
AU - Velculescu, Victor E.
AU - Kurman, Robert J.
AU - Wang, Tian Li
N1 - Funding Information:
Supported by grants RSG-08-174-01-GMC from the American Cancer Society , and the Ovarian Cancer Research Fund (T.L.W.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (V.V.); grants NTUH-98N1265 and NSC-98-2320-B-002-040 (K.T.K.); and grants CA103937 and CA129080 (I.M.S.), CA121113 (V.V.), and CA116184 (R.J.K.) from the National Institutes of Health .
PY - 2011/4
Y1 - 2011/4
N2 - Exome sequencing of ovarian clear-cell carcinoma has identified somatic mutations in PPP2R1A, a subunit of protein phosphatase 2A. The present study was performed to determine the frequency of PPP2R1A mutations in exon 5, which harbors previously reported mutation hot spots, and adjacent exon 6, in 209 ovarian and 56 uterine tumors of various histologic subtypes. PPP2R1A mutations were demonstrated in 10 of 110 type I ovarian tumors (9.1%) including low-grade serous, low-grade endometrioid, clear-cell, and mucinous carcinomas. In contrast, none of 71 type II ovarian (highgrade serous) carcinomas exhibited PPP2R1A mutations. Moreover, PPP2R1A mutations were observed in 2 of 30 type I uterine (endometrioid) carcinomas (6.7%) and 5 of 26 type II uterine (serous) carcinomas (19.2%). Of the 18 mutations, 13 affected the R182 or 183, and there were 5 novel mutations including 3 involving S256, 1 involving W257, and 1 involving P179. All mutations were located in the α-helix repeats near the interface between the A subunit and the regulatory B subunit of the enzyme complex. These data provide new evidence that PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas, and suggest that mutation of PPP2R1A may participate in the pathogenesis of ovarian type I and uterine type II carcinomas.
AB - Exome sequencing of ovarian clear-cell carcinoma has identified somatic mutations in PPP2R1A, a subunit of protein phosphatase 2A. The present study was performed to determine the frequency of PPP2R1A mutations in exon 5, which harbors previously reported mutation hot spots, and adjacent exon 6, in 209 ovarian and 56 uterine tumors of various histologic subtypes. PPP2R1A mutations were demonstrated in 10 of 110 type I ovarian tumors (9.1%) including low-grade serous, low-grade endometrioid, clear-cell, and mucinous carcinomas. In contrast, none of 71 type II ovarian (highgrade serous) carcinomas exhibited PPP2R1A mutations. Moreover, PPP2R1A mutations were observed in 2 of 30 type I uterine (endometrioid) carcinomas (6.7%) and 5 of 26 type II uterine (serous) carcinomas (19.2%). Of the 18 mutations, 13 affected the R182 or 183, and there were 5 novel mutations including 3 involving S256, 1 involving W257, and 1 involving P179. All mutations were located in the α-helix repeats near the interface between the A subunit and the regulatory B subunit of the enzyme complex. These data provide new evidence that PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas, and suggest that mutation of PPP2R1A may participate in the pathogenesis of ovarian type I and uterine type II carcinomas.
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U2 - 10.1016/j.ajpath.2011.01.009
DO - 10.1016/j.ajpath.2011.01.009
M3 - Article
C2 - 21435433
AN - SCOPUS:79953666737
SN - 0002-9440
VL - 178
SP - 1442
EP - 1447
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -