Abstract
Identifying cancer-specific biomarkers represents an ongoing challenge to the development of novel cancer diagnostic, prognostic and therapeutic strategies. Cancer/testis (CT) genes are an important gene family with expression tightly restricted to the testis in normal individuals but which can also be activated in cancers. Here we develop a pipeline to identify new CT genes. We analysed and validated expression profiles of human meiotic genes in normal and cancerous tissue followed by meta-analyses of clinical data sets from a range of tumour types resulting in the identification of a large cohort of highly specific cancer biomarker genes, including the recombination hot spot activator PRDM9 and the meiotic cohesin genes SMC1beta and RAD21L. These genes not only provide excellent cancer biomarkers for diagnostics and prognostics, but may serve as oncogenes and have excellent drug targeting potential.
Highlights
The demarcation of neoplastic cells from healthy tissue represents an important goal in clinical oncology; this is of particular interest given the need for diagnostic markers to enable early intervention strategies, such as surgical resection, and the re-emergence of immunotherapeutics, cancer vaccines and targeted drug delivery via antibody-drug conjugates [1,2,3,4,5,6,7,8,9,10]
As a first step to address the possibility that additional meiosis-specific genes might encode highly restricted Cancer/ testis (CT) antigens, we selected from the literature a sample cohort of human genes predicted to have meiosis-specific expression (Supplementary Table S1)
Despite the detection of REC8 and STAG3 expression in normal tissue, the other two meiosis cohesin genes tested, RAD21L and SMC1beta, exhibited a tight testis-specific expression profile (Fig. 1A). To explore whether these testis-specific cohesin genes could potentially encode CT antigens we analysed their expression using reverse transcriptase polymerase chain reaction (RT-PCR) on RNA samples taken from cancer cell lines and tumour samples from a range of cancer types
Summary
The demarcation of neoplastic cells from healthy tissue represents an important goal in clinical oncology; this is of particular interest given the need for diagnostic markers to enable early intervention strategies, such as surgical resection, and the re-emergence of immunotherapeutics, cancer vaccines and targeted drug delivery via antibody-drug conjugates [1,2,3,4,5,6,7,8,9,10] To achieve this goal, the identification of tumourassociated antigens is of central importance [for example, see 11-13]. Some CT antigens are present in other immunologically privileged tissues of the central nervous www.impactjournals.com/oncotarget system (CNS) and these are referred to as cancer/testisCNS (CT/CNS) antigens [25]
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