Blackwell Publishing Asia Frequent Alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 Region in Early and late-onset breast carcinoma: clinical and prognostic significance
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Blackwell Publishing Asia Frequent Alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 Region in Early and late-onset
breast carcinoma: clinical and prognostic significance
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| Creator |
Sinha, Satyabrata
Singh, Ratnesh K Alam, Neyaz Roy, Anup Roychoudhury, Susanta Panda, Chinmay Kumar |
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| Subject |
Molecular & Human Genetics
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| Description |
Young age can be an independent prognostic factor for adverse prognosis in women with breast carcinoma (BC). In younger women, BC exhibited more aggressive pathological features than older women, indicating differences in biology. Frequent alterations in chromosomal (chr.) 3p22.3 in different malignancies indicated the existence of multiple candidate tumor suppressor genes (TSG) in
this region, yet its association with BC remains unclear. In an effort to understand the differences in molecular pathogenesis in two age groups of BC, detailed analysis of alterations at chr.3p22.3 region was carried out in 47 early onset (group-A: 40 years) and 59 lateonset
(group-A: >40 years) BC samples. Deletion mapping of the
four candidate TSG, hMLH1, APRG1, ITGA9 and RBSP3/HYA22,
located within 1 Mb of chr.3p22.3 showed high deletion in hMLH1 and RBSP3/HYA22 genes. Frequent methylation was also observed in these genes and significantly associated with their deletion. Quantitative messenger RNA (mRNA) expression and immunohistochemical analysis showed down-regulation of these genes. Alterations (deletion/methylation) of hMLH1 were significantly
associated with RBSP3/HYA22 in group-A (P = 0.02). Significant poor survival in group-A patients with alterations in hMLH1 and RBSP3/ HYA22 and the same in group-B patients with hMLH1 alterations indicated their importance as prognostic markers. Differential
association of alterations of these genes with higher histological grades, more advanced stages and positive lymph node involvement were also seen. Thus, the present study suggests hMLH1 and RBSP3/HYA22 to be candidate TSG associated with development of both early and late-onset BC undergoing frequent genetic and epigenetic alteration and having significant prognostic implications.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/145/1/CANCER_SCIENCE%2C99(10)%2C1984%2D1991%2C2008[25].pdf
Sinha, Satyabrata and Singh, Ratnesh K and Alam, Neyaz and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay Kumar (2008) Blackwell Publishing Asia Frequent Alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 Region in Early and late-onset breast carcinoma: clinical and prognostic significance. Cancer Science, 99 (10). pp. 1984-1991. |
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| Relation |
http://dx.doi.org/10.1111/j.1349-7006.2008.00952.x
http://www.eprints.iicb.res.in/145/ |
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