Genetic and Epigenetic Aberrations of SOX7 in Newly Diagnosed and Relapsed Multiple Myeloma as Well as Related Neoplasms.

Multiple myeloma (MM) is one of the most frequent hematological malignancies. Most MM cases relapse, which is associated with poor prognosis. MM-related tumor suppressor genes are not totally known yet. SOX7 is one of the tumor suppressor candidates located in 8p23.1, a recurrently deleted region in MM. Here, we evaluated the genetic and epigenetic aberrancies of SOX7 in diagnostic or relapsed MM as well as smoldering MM (SMM) and plasma cell leukemia (PCL). Publicly available datasets were reanalyzed to evaluate SOX7 copy number, promoter methylation, transcript levels in MM or related neoplasms and to evaluate mutation rates in MM cases. qPCR and qRT-PCR with an in-house MM cohort were performed to cross-validate SOX7 copy number and transcript level estimates. SOX7 deletions were frequent in newly diagnosed and relapsed MM cases. SOX7 promoter hypermethylation was observed in MM cell lines, MM cases, and PCL cases. Importantly, SOX7 was transcriptionally silent in MM cell lines and underexpressed in MM and high-risk SMM cases. Integrative analyses of patient-matched diagnostic and relapsed MM tumor tissues revealed moderate positive correlations between SOX7 copy numbers. SOX7 deletion and promoter methylation levels had a tendency to be mutually exclusive. SOX7 promoter methylation levels were significantly higher in relapsed cases compared to the diagnostic ones. SOX7 mutations were rare in MM cases. SOX7 underexpression may be due to genetic and/or epigenetic alterations in newly diagnosed and relapsed MM. These genetic and epigenetic aberrations can serve as diagnostic or prognostic biomarkers for MM and allied neoplasms. Future research will reveal whether SOX7 inactivation has a role in development of these plasma cell neoplasms.