FAM 83 family oncogenes are broadly involved in human cancers: an integrative multi‐omics approach

The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM 83 (‘family with sequence similarity 83’) family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM 83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM 83 family members. We assessed transcriptional expression patterns of eight FAM 83 family genes ( FAM 83A‐H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival. By comparing the gene expression levels of FAM 83 family members in cancers from 17 different tumor types with those in their corresponding normal tissues, we identified consistent upregulation of FAM 83D and FAM 83H across the majority of tumor types, which is largely driven by increased DNA copy number. Importantly, we found also that a higher expression level of a signature of FAM 83 family members was associated with poor prognosis in a number of human cancers. In breast cancer, we found that alterations in FAM 83 family genes correlated significantly with TP 53 mutation, whereas significant, but inverse correlation was observed with PIK 3 CA and CDH 1 (E‐cadherin) mutations. We also identified that expression levels of 55 proteins were significantly associated with alterations in FAM 83 family genes including a decrease in GATA 3, ESR 1, and PGR proteins in tumors with alterations in FAM 83. Our results provide strong evidence for a critical role of FAM 83 family genes in tumor development, with possible relevance for therapeutic target development.