Germline large genomic alterations on 7q in patients with multiple primary cancers

Abstract

Patients with multiple primary cancers (MPCs) are suspected to have a hereditary cancer syndrome. However, only a small proportion may be explained by mutations in high-penetrance genes. We investigate two unrelated MPC patients that met Hereditary Breast and Ovaria Cancer criteria, both presenting triple negative breast tumors and no mutations in BRCA1, BRCA2 and TP53 genes. Germline rearrangements on chromosome 7q, involving over 40 Mb of the same region, were found in both patients: one with mosaic loss (80% of cells) and the other with cnLOH (copy-neutral loss of heterozygosity) secondary to maternal allele duplication. Five children tested had no alterations on 7q. The patients shared 330 genes in common on 7q22.1-q34, including several tumor suppressor genes (TSGs) previously related to breast cancer risk and imprinted genes. The analysis of the triple negative BC from one patient revealed a mosaic gain of 7q translated for over-expressed cancer-related genes. The involvement of TSGs and imprinted genes, mapped on 7q, has the potential of being associated to MPC risk, as well as cancer progression. To our knowledge, this is the first description of patients with MPCs that harbor constitutive large alterations on 7q.

Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies

“…Copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) were assessed using the CytoScan HD platform (Thermo Fisher Scientific, Waltham, MA, USA). Data were analyzed with the Chromosome Analysis Suite 3.0 (ChAS) software (Thermo Fisher Scientific, Waltham, MA, USA, v.4.0), considering at least 25 markers for losses/mosaic losses, 50 markers for gains/mosaic gains, and cnLOHs with a minimum of 5 Mb, as previously described [25,26]. A distogram showing dissimilarity between samples (matched primary tumor and cell culture) was performed using the R package Rawcopy [27].…”