Assessment of the quality and frequency of mutations occurrence in PTEN gene in endometrial carcinomas and hyperplasias

Konopka, B; Paszko, Z; Janiec–Jankowska, Aneta; Goluda, M

doi:10.1016/s0304-3835(01)00815-1

Cited by 41 publications

(32 citation statements)

References 17 publications

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“…PTEN exhibits combined LOH of one allele and mutation in the other allele at frequencies up to 50% in human endometrial tumors. PTEN mutations have even been detected in 33-55% of the endometrial precancerous lesions (Risinger et al 1997, 1998, Tashiro et al 1997, Konopka et al 2002, Latta & Chapman 2002. We found no sequence alterations in the entire coding region of the Pten gene in any of the BDII rat tumors.…”

Section: Discussionsupporting

confidence: 43%

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Samuelson

Hedberg²,

Nilsson³

et al. 2009

Endocrine-Related Cancer

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Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (b-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.

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Section: Discussionsupporting

confidence: 43%

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Samuelson

Hedberg²,

Nilsson³

et al. 2009

Endocrine-Related Cancer

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“…For PTEN gene, most identified mutations were present in exons 5, 6, 7, and 8, especially exon 5, in human cancers (25,26). Therefore, we selected these exons of PTEN gene for mutation analysis in this study.…”

Section: Methodsmentioning

confidence: 99%

Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer

Hou¹,

Liu²,

Yuan³

et al. 2007

Clinical Cancer Research

365

306

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Purpose:To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. Experimental Design: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. Results: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/ Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. Conclusions: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway^related genetic alterations and BRAF mutation.The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers.

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“…It is now generally accepted that mutations of the PTEN tumor suppressor gene play a critical role in an early development of the endometrial carcinoma (Mutter 2002). Our previous studies have shown that PTEN gene mutations are observed in about 50% of these carcinomas (Konopka et al 2002). Given that not all endometrial carcinomas have PTEN mutations, it appears that other genetic defects are involved in the development and progression of these tumors.…”

Section: Introductionmentioning

confidence: 96%

The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma

Konopka

Janiec–Jankowska

Paszko

et al. 2004

Journal of Cancer Research and Clinical Oncology

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Our data suggest that differences in the presence of genetic defects may reflect the different molecular pathways of endometrial carcinogenesis. These data also suggest that location of intragenic PTEN mutations and their coexistence with the CMYC amplification may play a crucial part in the development of various subtypes of endometrial carcinoma, but this preliminary suggestion requires further research.

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Assessment of the quality and frequency of mutations occurrence in PTEN gene in endometrial carcinomas and hyperplasias

Cited by 41 publications

References 17 publications

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer

The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma

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