Identification and Characterization of Molecular Abnormalities of 11p Genes in Human Breast Cancer
Final rept. 1 Oct 94-28 Feb 99
JOHNS HOPKINS UNIV BALTIMORE MD
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We have been investigating the hypothesis that 11p15 harbors one or more breast cancer suppressor genes. We have defined a minimal region of loss of heterozygosity in breast cancer between D11S988 and D11S1318. We have also performed genetic complementation experiments on breast cancer cells using subchromosomal transferable fragments STF, but the STFs did not prove to be sufficiently stable for these cells. We have therefore developed a novel one-step retrofitting vector containing a mammalian selectable gene that allows us to modify bacterial artificial chromosome BAC for genetic complementation experiments, and we have successfully introduced these into tumor cells. We are currently testing these modified BACs on MCF-7 and HuMi breast cancer cells. We have also identified two new candidate genes within the region of LOH, termed TSSC4 and TSSC6. Twelve to 98 breast cancer samples were sequenced over the entire coding sequence of 8 genes within the region of LOH. While no somatic mutations were found, we did observe a germline alteration of one gene with in a patient multiple primary breast cancers. In addition, we found a novel alteration, relaxation of splicing fidelity, affecting multiple genes, in over half of human breast cancers.
- Anatomy and Physiology
- Medicine and Medical Research