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.
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.
Authors: Kumud R Poudel; Minna Roh-Johnson; Allen Su; Thuong Ho; Haritha Mathsyaraja; Sarah Anderson; William M Grady; Cecilia B Moens; Maralice Conacci-Sorrell; Robert N Eisenman; Jihong Bai Journal: Dev Cell Date: 2018-06-18 Impact factor: 12.270
Authors: Santanu Dasgupta; Jin Sung Jang; Chunbo Shao; Nitai D Mukhopadhyay; Upneet K Sokhi; Swadesh K Das; Mariana Brait; Conover Talbot; Rex C Yung; Shahnaz Begum; William H Westra; Mohammad Obaidul Hoque; Ping Yang; Joanne E Yi; Stephan Lam; Adi F Gazdar; Paul B Fisher; Jin Jen; David Sidransky Journal: J Mol Med (Berl) Date: 2012-09-12 Impact factor: 4.599
Authors: Shyama Majumdar; Edward M Gong; Dolores Di Vizio; Jonathan Dreyfuss; David J Degraff; Martin H Hager; Peter J Park; Joaquim Bellmunt; Robert J Matusik; Jonathan E Rosenberg; Rosalyn M Adam Journal: Neoplasia Date: 2013-07 Impact factor: 5.715