Breast carcinomas are characterized by DNA copy number alterations
(CNAs) with biological and clinical significance. This explorative study
integrated CNA, expression, and germline genotype data of 112
early‐stage breast cancer patients. Recurrent CNAs differed
substantially between tumor subtypes classified according to expression
pattern. Deletion of 16q was overrepresented in Luminal A, and a
predictor of good prognosis, both overall and for the nonluminal A
subgroups. The deleted region most significantly associated with
survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38,
whose expression was strongly correlated with the deletion. The area
most frequently deleted resided on 16q23.1, 3.5 MB downstream of the
area most significantly associated with survival, and included the tumor
suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4.
Whole‐genome association analysis identified germline single nucleotide
polymorphisms (SNPs) and their corresponding haplotypes, residing on
several different chromosomes, to be associated with deletion of 16q.
The genes where these SNPs reside encode proteins involved in the
extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).
- breast cancer
- gene expression