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01-04-2008 | Breast Oncology

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

Authors: Satyabrata Sinha, MSc, Neelanjana Chunder, PhD, Nupur Mukherjee, MSc, Neyaz Alam, MS, Anup Roy, MD, Susanta Roychoudhury, PhD, Chinmay Kumar Panda, PhD

Published in: Annals of Surgical Oncology | Issue 4/2008

Abstract

Background

This study attempts to understand the association of candidate tumour suppressor genes SH3GL2, CDKN2A (p16–p14) and CDKN2B (p15) in development of early-onset (group A) and late-onset (group B) breast carcinoma (BC).

Methods

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.

Results

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.

Conclusions

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.

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Title: Frequent Deletion and Methylation in SH3GL2 and CDKN2A Loci are Associated with Early- and Late-onset Breast Carcinoma
Authors: Satyabrata Sinha, MSc
Neelanjana Chunder, PhD
Nupur Mukherjee, MSc
Neyaz Alam, MS
Anup Roy, MD
Susanta Roychoudhury, PhD
Chinmay Kumar Panda, PhD
Publication date: 01-04-2008
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 4/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-007-9790-0

At a glance: The ONWARDS insulin icodec trials

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

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Abstract

Background

Methods

Results

Conclusions

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