Analysis of different deleted regions in chromosome 11 and their interrelations in early and late onset breast tumors: association with cyclin D1 amplification and survival

Abstract

Previous studies have shown that younger women exhibit more aggressive pathologic features of breast cancer (BC) in comparison to older women; young age could be an independent predictor of adverse prognosis. In order to find any existing differences in the molecular progression of BC in both younger and older women, chromosome 11 (chr.11) was taken as a tool, due to its frequent deletion and amplification, particularly of CyclinD1 (CCND1) locus in BC. In the present work, the comparative analysis in the frequency of deletion in different regions in chr.11 and CCND1 amplification in BC in the two age groups was studied, as well as the interrelation and prognostic significance of these chromosomal alterations. The chr. 11 alterations were also studied in types of breast lesions other than carcinoma to see the prevalence of the alterations in these diseases. For this purpose, comparative deletion mapping of chr.11 using 17 microsatellite markers and CCND1 amplification was examined in 30 early-onset (≤40 years) and 33 late-onset (>40 years) breast carcinomas, as well as 11 other types of breast lesions. The frequency of deletion and CCND1 amplification was much higher in carcinomas than with other types of breast lesions. A total of six highly deleted regions, namely, 11p15.5, 11p11.2, 11q13.2, 11q22.3-23.1, 11q23.3-24.1, and 11q25, were identified in carcinomas of the two age groups. The 11q13.2 deletion and CCND1 amplification was comparatively higher in the carcinoma of younger women. The following significant associations were observed for (a) LOH at 11q25 with LOH at 11q13.2, 11q22.3-23.1, 11q23.3-24.1 and CCND1 amplification, respectively, and (b) LOH at 11p15.5 with LOH at 11q22.3-23.1 in carcinoma of younger women. On the other hand, the significant associations in older women were (a) LOH at 11q25 with LOH at 11q22.3-23.1, 11q23.3-24.1, respectively, and (b) LOH at 11q22.3-23.1 with LOH at 11q23.3-24.1. Deletion at 11q13.2 was also associated with reduced overall survival in the younger group, indicating its prognostic significance. It is evident from our data that the pattern of chromosomal alterations are not exactly same in the carcinomas in the two age groups. Differential interrelationship of the chromosomal alterations and prognosis in these two age groups indicate that the molecular pathogenesis of the carcinomas is not similar.