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Frequent Deletion and Methylation in SH3GL2 and CDKN2A Loci are Associated with Early- and Late-onset Breast Carcinoma

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Title Frequent Deletion and Methylation in SH3GL2
and CDKN2A Loci are Associated with Early- and Late-onset
Breast Carcinoma
 
Creator Sinha, Satyabrata
Chunder, Neelanjana
Mukherjee, Nupur
Alam, Neyaz
Roy, Anup
Roychoudhury, Susanta
Panda, Chinmay Kumar
 
Subject Molecular & Human Genetics
 
Description This study attempts to understand the association of candidate tumour suppressor
genes SH3GL2, CDKN2A (p16–p14) and CDKN2B (p15) in development of earlyonset
(group A) and late-onset (group B) breast carcinoma (BC). Deletion, methylation, and mutation of the candidate tumour suppressor genes
(TSGs) were analysed in 47 group A and 59 group B samples. Immunohistochemical analysis
was used to identify the expression status of SH3GL2 and p16. Clinicopathological correlation
of the alterations was analysed by the chi-square and log-rank tests.
Higher frequency of overall alterations (46–62%) in SH3GL2 and p16-p14 than
p15 (22–26%) indicated their importance in BC. Deletion frequencies were in the following
order: group A: p14 (43%) > p16 (42%) > SH3GL2 (38%) > p15 (33%) and group B: p14
(36%) > p16 (33%) > SH3GL2 (31%) > p15 (14%) while, methylation frequencies were:
group A: SH3GL2 (34%) > p16 (28%) > p14 (26%) > p15 (15%) and group B: SH3GL2
(36%) > p16 (31%) > p14 (29%) > p15 (15%). Infrequent mutation was observed only in
CDKN2A common exon-2. Immunohistochemical analysis showed significant association
between expression of SH3GL2 and p16 with their deletion (P = 0.01 and 0.02, respectively)
and methylation status (P = 0.007 and 0.01, respectively). In group A, overall alterations of
SH3GL2 showed significant association with CDKN2A locus with significant prognostic
implications, whereas CDKN2A and CDKN2B loci were associated in both groups.The molecular mechanisms involving CDKN2A inactivation seem to follow
similar pathway in the pathogenesis of both age groups of BC while significant association of
SH3GL2 with CDKN2A might play a synergistic role in the development of group A.
 
Publisher Lippincott, Williams & Wilkins
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/274/1/ANNALS_OF_SURGICAL_ONCOLOGY%2C15(_4)%2C_1070%2D1080%2C2008[108].pdf
Sinha, Satyabrata and Chunder, Neelanjana and Mukherjee, Nupur and Alam, Neyaz and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay Kumar (2009) Frequent Deletion and Methylation in SH3GL2 and CDKN2A Loci are Associated with Early- and Late-onset Breast Carcinoma. Annals of Surgical Oncology, 15 (4). pp. 1070-1080. ISSN 1068-9265
 
Relation http://dx.doi.org/10.1245/s10434-007-9790-0
http://www.eprints.iicb.res.in/274/