Recurrent allelic imbalance at the rat <i>Pten</i> locus in DMBA‐induced fibrosarcomas

Sjöling, Åsa; Samuelson, Emma; Adamović, Tatjana; Behboudi, Afrouz; Röhme, Dan; Levan, Göran

doi:10.1002/gcc.10143

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Taken together, these results suggest that Pten is likely involved in tumorigenesis of BDII rat EAC. Similar conclusions regarding Pten functioning in a Endocrine-Related Cancer (2009) 16 99-111 www.endocrinology-journals.org haploinsufficient mode has been drawn in several other reports (Di Cristofano et al 1998, Kwabi-Addo et al 2001, Sjöling et al 2002, Kolasa et al 2006, Kwon et al 2008. Decreasing level of PTEN expression was shown to correlate with the progressive outcome of solid cancers, including ovarian, prostate, and cervical cancers (Harima et al 2001, Jiang & Liu 2008.…”

Section: Discussionsupporting

confidence: 74%

“…The Pten intragenic marker D1Lev1 (Sjöling et al 2002) is informative between the BDII and SPRD strain animals, but not between BDII and BN rats. The D1Lev1 marker was used in conjunction with another informative microsatellite marker (D1Rat81) for AI scoring of Pten locus in animals of the SPRD cross.…”

Section: Allelic Imbalance Analysis and Mutation Sequencing Of The Ptmentioning

confidence: 98%

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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: 74%

Section: Allelic Imbalance Analysis and Mutation Sequencing Of The Ptmentioning

confidence: 98%

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

Samuelson

Hedberg²,

Nilsson³

et al. 2009

Endocrine-Related Cancer

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“…In this study, we demonstrated that the PTEN mutation in STS in Chinese patients, at a frequency of 2.3%, is rare. Their mutation frequency and distribution were consistent with previous reports (22,29,30). In this study, we used PCR-SSCP and DNA sequencing techniques to investigate the sequences of exons 5-8, which were frequently mutated in 86 STS cases.…”

Section: Discussionsupporting

confidence: 87%

Mutational analysis of p53 and PTEN in soft tissue sarcoma

2011

Mol Med Report

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Abstract. p53 and PTEN are the two most frequently mutated tumor suppressors in human cancer. However, literature on the effect of the joint inactivation of tumor-suppressor genes in soft tissue sarcoma (STS) is lacking. The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis. We screened mutations of p53 and PTEN in 86 human STSs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, respectively. p53 mutations were detected in 25.6% (22 out of 86) of STSs: 6 cases of p53 mutations were detected in 46 cases of specific reciprocal translocations in STSs (13.0%), 16 cases were detected in 40 cases of nonspecific reciprocal translocations in STSs (40.0%); the majority of the mutations were point mutations in exon 6-7. Furthermore, PTEN mutations were observed in 2 out of 86 STSs (2.3%). Two out of 86 cases revealed a 130th codon G>A missense mutation in exon 8 of PTEN which resulted in an Arg change to Gln in the PTEN protein structure; and a 334th codon A>T missense mutation in exon 8 of PTEN, which resulted in an Asn change to Lys in the PTEN protein structure. All subjects were examined for p53 exon 5-9 mutations and for PTEN exon 5-9 mutations. However, no tumors contained an alteration of the two genes. The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations. Although the existence of PTEN mutations in STS was detected, the PTEN mutation frequency was quite low. We conclude that PTEN may have played a less prognostic role than p53 in the development and malignant transformation of STS in the patients examined. IntroductionSomatic mutations of tumor-suppressor genes and oncogenes are the most common genetic alterations found in human malignancies. p53 plays a major role in regulating the response of mammalian cells to stresses and damage, in part, through the transcriptional activation of genes involved in cell cycle control, DNA repair, senescence, angiogenesis and apoptosis (1,2). Deletions or point mutations in p53 are prevalent in the majority of types of human cancer (3,4). Furthermore, mutations in p53 have also been identified as the most common genetic alterations in soft tissue sarcoma (STS) (5).PTEN, a phosphatase with specificity for lipids and proteins, is involved in basic cellular functions including adhesion, migration, proliferation and cell survival (6). PTEN is a tumor-suppressor gene located on chromosome 10q23.3, and somatic mutations in PTEN are now known to cause tumorigenesis in a number of human tissues (7). Germline mutations of PTEN are associated with inherited Cowden and Bannayan-Riley-Ruvalcuba syndromes, which are characterized by multiple benign tumors and with enhanced risk of breast and thyroid cancers...

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“…Although loss of one functional Pten allele was found in 68% of prostate tumors from Pten þ /À mice and in 47.4% of tumors from wild-type mice, no evidence for any specific intragenic mutations was found in any of these tumors. To our knowledge, no examples exist of intragenic mutations in any mouse (Kwabi-Addo et al, 1998) or rat (Sjoling et al, 2003) models involving LOH at the Pten locus. The situation we have seen in mouse lymphomas more closely resembles that seen in human tumors, in that we see a proportion of small localized changes within the Pten gene, but in only rare cases are these homozygous.…”

Section: Discussionmentioning

confidence: 99%