High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.

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dc.contributor.authorGupta, S
dc.contributor.authorJoshi, K
dc.contributor.authorWig, J D
dc.contributor.authorArora, S K
dc.date.accessioned2013-01-10T08:15:04Z
dc.date.available2013-01-10T08:15:04Z
dc.date.issued2009-10
dc.description.abstractBackground: The product of Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression. Methods: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-β1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma. Results: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-β1, VEGF expression and IMD scores in infiltrating carcinoma. Conclusions: The current study indicates that the high frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.en_US
dc.identifier.citationGupta S, Joshi K, Wig J D, Arora S K. High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor. Indian Journal of Cancer. 2009 Oct-Dec; 46(4): 303-310.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/144266
dc.language.isoenen_US
dc.source.urihttps://www.indianjcancer.com/article.asp?issn=0019-509X;year=2009;volume=46;issue=4;spage=303;epage=310;aulast=Guptaen_US
dc.subjectDuctal carcinoma in situen_US
dc.subjectinsulin-like growth factor IIen_US
dc.subjecttransforming growth factor βen_US
dc.subjectvascular endothelial growth factoren_US
dc.subjectWilms′ tumor suppressor geneen_US
dc.subject.meshBreast Neoplasms --genetics
dc.subject.meshBreast Neoplasms --pathology
dc.subject.meshCarcinoma in Situ --genetics
dc.subject.meshCarcinoma in Situ --pathology
dc.subject.meshCarcinoma, Ductal, Breast --genetics
dc.subject.meshCarcinoma, Ductal, Breast --pathology
dc.subject.meshGenes, Wilms Tumor
dc.subject.meshHumans
dc.subject.meshInsulin-Like Growth Factor II --biosynthesis
dc.subject.meshLoss of Heterozygosity
dc.subject.meshPolymerase Chain Reaction
dc.subject.meshPolymorphism, Restriction Fragment Length
dc.subject.meshReceptor, IGF Type 1 --biosynthesis
dc.subject.meshTransforming Growth Factor beta1 --biosynthesis
dc.subject.meshVascular Endothelial Growth Factor A --biosynthesis
dc.titleHigh frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.en_US
dc.typeArticleen_US
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