PTEN1 is frequently mutated in primary endometrial carcinomas

Kong, Dehe; Suzuki, Akihiko; Zou, Tong; Sakurada, Akira; Kemp, Lawrence W.; Wakatsuki, Shigeru; Yokoyama, Toshiharu; Yamakawa, Hiromitsu; Furukawa, Toru; Sato, Masami; Ohuchi, Noriaki; Sato, Shinji; Yin, Jing; Wang, Suna; Abraham, John M.; Souza, Rhonda F.; Smolinski, Kara N.; Meltzer, Stephen J.; Horii, Akira

doi:10.1038/ng1097-143

Cited by 301 publications

(235 citation statements)

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“…PTEN1 mutations were also observed in gliomas without severe MSI, demonstrating that loss of the PTEN1 product could play an important role in tumor formation in both gliomas with and without MSI. Mutation of the PTEN1 gene has also been reported in both MSI-positive and MSI-negative endometrial cancers (Kong et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, slippage mutations of the TGFb RII and BAX genes at their mononucleotide repeat sequences have been detected almost exclusively in colon cancers with MSI (Markowitz et al, 1995;Rampino et al, 1997). Deletion or insertion of one to several base pairs within the microsatellite sequences of the IGFIIR, E2F4 or PTEN1 gene was also reported in colorectal cancers or endometrial cancers with MSI (Rampino, et al, 1997;Yoshitaka et al, 1996;Kong et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene

et al. 2000

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“…Studies also revealed that the PTEN/MMAC1 gene was highly mutated in glioblastomas Wang et al, 1997;Rasheed et al, 1997;Liu et al, 1997), melanoma (Guldberg et al, 1997), and endometrial carcinomas (Tashiro et al, 1997;Kong et al, 1997). To examine whether the PTEN/MMAC1 gene is a target of the 10q loss in SCLC, and to understand the role of the PTEN/MMAC1 gene in various kinds of lung cancers, we screened 34 SCLC cell lines, 10 SCLC tissues, 13 NSCLC cell lines and 10 NSCLC tissues to detect alterations in the PTEN/ MMAC1 gene at the genomic DNA level.…”

Section: Introductionmentioning

confidence: 99%

PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers

et al. 1998

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A putative tumor suppressor, PTEN/MMAC1 gene at 10q23 was recently identi®ed and found to be mutated in many di erent human tumors. To determine the role of the PTEN/MMAC1 gene in lung cancer, we screened 34 small cell lung cancer (SCLC) cell lines, 10 SCLC tumors, 13 non-small cell lung cancer (NSCLC) cell lines and 10 NSCLC tumors using Denaturing HPLC (DHPLC) and direct sequencing methods. In SCLC, six (18%) of the cell lines and one of the primary tumor samples (10%) showed alterations of the PTEN/ MMAC1 gene including point mutations, small fragment deletions, and homozygous deletions. All of the point mutations and small fragment deletions were observed in hemizygously deleted cell lines. In contrast to SCLC, none of the NSCLC tumors or cell lines had mutations in the PTEN/MMAC1 gene. These data indicate that PTEN/MMAC1 mutations contribute to the pathogenesis and neoplastic evolution in SCLC but not in NSCLC.

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“…Patients with high-grade tumors that invade 41/2 of the myometrial thickness or exhibit lymphovascular invasion have a high risk of regional lymph node metastases and require adjuvant therapy. 2 Within the last decade, several genetic alterations, including microsatellite instability, [3][4][5] PTEN alterations, [6][7][8] and mutations of K-RAS 9-11 and CTNNB1 (b-catenin), 12,13 have been discovered in endometrioid adenocarcinomas and their prognostic significance widely investigated. Although microsatellite instability was initially thought to be associated with a favorable outcome, 14 recent data, obtained after excluding nonendometrioid carcinomas, have shown that the frequency of microsatellite instability is higher in high-grade and advanced stage tumors with deep myometrial and lymphovascular invasion.…”

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confidence: 99%

PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters

et al. 2008

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Mutations of the oncogene PIK3CA occur frequently in endometrial carcinomas, but their prognostic significance is unclear. To determine the clinicopathological and molecular implications of these mutations, PIK3CA status was investigated in 109 endometrial (102 endometrioid and 7 mixed) carcinomas and the results were compared with clinicopathological parameters associated with prognosis. Tumors were also investigated for microsatellite instability and PTEN, b-catenin gene (CTNNB1), K-RAS, and B-RAF mutations. We found 35 PIK3CA somatic missense mutations in 32 (29%) endometrial carcinomas. Eighteen mutations occurred in exon 20 (kinase domain), and 17 in exon 9 (helical domain). Almost all mutated tumors were pure endometrioid adenocarcinomas. All tumors with PIK3CA mutations exhibited myometrial invasion (P ¼ 0.032). Lymphovascular invasion was found more frequently in mutated (28%) than nonmutated carcinomas (18%). Histological grade varied significantly according to the location of the PIK3CA mutations whether in exon 9 or exon 20 (P ¼ 0.033). The frequency of exon 9 mutations was higher in grade 1 carcinomas (57%) than in grade 2 (29%) or grade 3 (14%) tumors. Conversely, mutations in exon 20 were more common in grade 3 (60%) than in grade 2 (20%) or grade 1 (20%) carcinomas. None of the tumors confined to the endometrium (stage IA) had PIK3CA mutations. Furthermore, whereas 64% of adenocarcinomas with exon 9 mutations had invaded r1/2 of the myometrial thickness (stage IB), 73% of tumors with exon 20 mutations had either deeper myometrial invasion (stage IC) or cervical involvement (stage II) (P ¼ 0.045). PIK3CA mutations coexisted with microsatellite instability and mutations in PTEN, CTNNB1, K-RAS, and B-RAF genes. These results favor that PIK3CA mutations are associated with myometrial invasion and, moreover, that tumors harboring PIK3CA mutations in exon 20 are frequently high-grade, deeply invasive endometrial carcinomas that tend to exhibit lymphovascular invasion.

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PTEN1 is frequently mutated in primary endometrial carcinomas

Cited by 301 publications

References 4 publications

Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene

Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene

PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers

PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters

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