CONICET | Buscador de Institutos y Recursos Humanos

The Heat Shock Proteins (HSP) are important in cancer development, progression and some are targets for anticancer therapy. The HSP genes are evolutionary conserved and the expression of the different members is variable. A comprehensive study of HSP mutations in different cancers is lacking. The purpose of this work is the mutational profile analysis of HSP in breast, prostate and ovarian cancers. The data were retrieved from the TCGA. We examined the mutations in the complete HSP family genes in 3 different tumor types and compared the HSP mutations with the top 10 mutations of the genome. The Mutation Annotation Format files, which contained somatic or germline mutations generated from whole exome sequencing were downloaded. We observed that mutations in the whole genome appeared in 84% of the breast cancer samples: TP53 (34%), PI3K (33%), TTN (19%), and CDH1 (14%) while the HSP mutations were observed in 8% of the samples: SACS (2%), DNAJC13 (2%) and BBS10 (1%). In prostate cancer mutations appeared in 43% of the samples: TP53 (11%), SPOP (10%) and TTN (9%), while the HSP mutations were infrequent appearing in 5% of the samples: SACS (5%), HSPA8 (1%), DNAJC13 (1%) and HSPA4 (1%). A high level of gene mutations appeared in ovarian carcinomas, in 94% of the samples: TP53 (88%), TTN (34%) and MUC16 (12%), while the HSP mutations were relatively infrequent appearing in 13% of the samples: SACS (4%), DNAJC11 (2%), and DNAJC14 (2%). Genomic Analysis of Important Aberrations (GAIA), was used to figure out the most significant recurrent CNV in the HSPs. No significant amplification or deletions were observed in HSPs.Our study revealed that mutations in HSP genes occurred at low frequencies and abnormalities in CNV cannot explain the HSP expression variability observed.