Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues

The Cub and Sushi Multiple Domains-1 (CSMD1) is a tumor suppressor gene on 8p23.2, where allelic loss is both frequent and associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). To understand the extent of CSMD1 aberrations in vivo, we characterized 184 primary tumors from the head and neck, lung, breast and skin for gene copy number and analyzed expression in our HNSCCs and lung squamous cell carcinomas (SCCs). We detected loss of CSMD1 in a large proportion of HNSCCs (50%), lung (46%) and breast cancers (55%), and to a lesser extent in cutaneous SCCs (29%) and basal cell carcinomas (BCCs, 17%) using array-based comparative genomic hybridization (aCGH). Studying the region more closely with quantitative real-time PCR (qPCR), the loss of CSMD1 increased to 80% in HNSCCs and 93% in lung SCCs. CSMD1 expression was decreased in tumors compared to adjacent benign tissue (65%, 13/20) and was likely due to gene loss in 45% of cases (9/20). We also identified truncated transcripts lacking exons due to DNA copy number loss (30%, 5/17) or aberrant splicing (24%, 4/17). We show loss of CSMD1 in primary HNSCC tissues, and document for the first time that CSMD1 is lost in breast, lung and cutaneous SCCs. We also show that deletions of CSMD1 and aberrant splicing contribute to altered CSMD1 function in vivo.