CHARACTERIZATION OF THE TRANSLOCATION BREAKPOINT INVOLVING CHROMOSOMES 4 AND 7, AN ABERRATION OBSERVED IN MURINE HORMONE-INDEPENDENT (HI) MAMMARY CARCINOMAS

VICTORIA T. FABRIS; SEBASTIÁN GIULIANELLI; PAOLA ROJAS; SUSANA MERANI; CLAUDIA LANARI

Denver, Colorado. USA.

Congreso; 100th AACR Annual Meeting; 2009

AACR

The cytogenetic analysis of the murine mammary carcinomas induced by medroxyprogesterone acetate (MPA) revealed the presence of chromosome aberrations, including different translocations. We observed a similar translocation between the chromosomes 4 and 7, T(4;7), in two different HI tumors (C7-2-HI and C4-HI). The aim of this study was to identify the breakpoint of this translocation T(4;7). For this purpose we used the MC7-L2A cell line which is derived from the C7-2-HI tumor, and retains the T(4;7) translocation. Fluorescent in situ hybridization (FISH) was used with specific sequences of DNA as probes on metaphases obtained from MC7-L2A cells. These probes hybridized to different regions of chromosomes 4 and 7. Previous G-banding data showed that the breakpoint could be located near the centromere of chromosome 7 (7A1-7B1), and the terminal portion of chromosome 4 (4E1-4E2). The probes corresponding to chromosome 7A2-7B1 hybridized to normal chromosome 7 and to the translocation T(4;7). The probe for chromosome band 7A1 only hybridized to the normal chromosome, but not to the translocation. The probe located on the band 4E1 hybridized to both, normal chromosome 4 and the translocation. These results indicate that the breakpoint of T(4;7) is located on the chromosome 7A1-7A2, and on the chromosome 4E2. Several genes mapping near the breakpoint on chromosome 7A1-7A2 have been involved in different types of tumors. We found in a DNA array comparing hormone-dependent and independent mammary tumors that the genes Sepw1 (Selenoprotein W, muscle 1), Ehd2 (EH-domain containing 2), and Bbc3 (BCL2 binding component 3), located on the region 7A2, are highly expressed in HI tumors. These genes are candidate genes that could be altered by the translocation T(4;7), and could participate in HI tumor growth.