Presence of Two Members of c-erbA Receptor Gene Family (c-erbAbeta and c-erbA2) in Smallest Region of Somatic Homozygosity on Chromosome 3p21-p25 in Human Breast Carcinoma

Abstract

The loss of heterozygosity of genes on the short arm of chromosome 3 (3p) in human breast carcinomas occurs in a region involved in other malignancies, including renal cell carcinoma, lung cancers, and von Hippel-Lindau disease. This finding suggests the presence of a gene(s) that plays a crucial role in multiple cancers. In our study of 84 informative (heterozygous) primary breast tumors, 30% showed losses of heterozygosity on chromosome 3. The shortest region of homozygosity in primary human breast tumor is located between the DNF15S2 and RAF1 loci in the 3p21–p25 region on the short arm of chromosome 3. This region includes at least two members of the c-erbA steroid/thyroid hormone receptor family (c-erbAβ and c-erbA2) that may be of special relevance to breast cancer. Furthermore, tumors with a loss of heterozygosity of genes on chromosome 3 were previously reported to have frequent allelic deletions on chromosome 11p and amplification of the c-mycproto-oncogene. These results highlight the occurrence of multiple genetic alterations in breast tumors. [J Natl Cancer Inst 81:1815–1820, 1989]