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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgements

We are thankful to the Director, Chittaranjan National Cancer Institute, Kolkata-700026, India. Financial support was provided by CSIR grant no. 60(0077)/06/EMR-II to Dr. C. K. Panda and CSIR–JRF/NET Fellowship grant no. 9/30(031)/2002- EMR-I to Mr. S. Sinha.

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Authors and Affiliations

  1. Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India

    Satyabrata Sinha MSc, Nupur Mukherjee MSc & Chinmay Kumar Panda PhD

  2. Department of Pathology, The Joseph Stokes, Jr. Research Institute, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Neelanjana Chunder PhD

  3. Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India

    Neyaz Alam MS

  4. Department of Pathology, Medical College, Kolkata, India

    Anup Roy MD

  5. Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India

    Susanta Roychoudhury PhD

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  1. Satyabrata Sinha MSc
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Correspondence to Chinmay Kumar Panda PhD.

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Sinha, S., Chunder, N., Mukherjee, N. et al. Frequent Deletion and Methylation in SH3GL2 and CDKN2A Loci are Associated with Early- and Late-onset Breast Carcinoma. Ann Surg Oncol 15, 1070–1080 (2008). https://doi.org/10.1245/s10434-007-9790-0

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