Genomics

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Post-zygotic structural variants in histologically normal breast tissue may predispose to sporadic breast cancer [SET 8]


ABSTRACT: Sporadic breast cancer (SBC) is a common and heterogeneous disease. There is no reliable way of early prediction of risk for SBC in the general population. We studied 282 females with SBC concentrating on copy number aberrations in tumor-free breast tissue (uninvolved margin, UM) outside the area of primary tumor (PT). Totally 1162 UMs (1-14 per breast) were studied. PT and blood/skin as control was also analyzed. Comparative analysis between genetic profiles for UM(s), PT(s) and blood/skin from the same patient is the core of study design. We identified 108 patients with at least one aberrant UM specimen, representing 38.3% of all cases. Gains were the dominating mutations in microscopically normal breast cells and gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional receptor genes (EGFR, FGFR1, IGF1R, LIFR and NGFR) also showed gains, and these were occasionally present in combination with the gain of ERBB2. Up to 67.6% of patients showed gain of one or more of these genes in normal cells. The aberrations found in normal cells from UMs were previously described in cancer literature, which suggest their causative, driving role in this disease. We demonstrate that analysis of normal cells from cancer-bearing patients leads to identification of genetic signatures that may predispose to SBC. Early detection of signals suggesting a predisposition towards development of SBC, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine of breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE64726 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA271754

REPOSITORIES: GEO

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