AUTHOR=Iqbal Waleed , Demidova Elena V. , Serrao Samantha , ValizadehAslani Taha , Rosen Gail , Arora Sanjeevani 

TITLE=RRM2B Is Frequently Amplified Across Multiple Tumor Types: Implications for DNA Repair, Cellular Survival, and Cancer Therapy

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.628758

DOI=10.3389/fgene.2021.628758

ISSN=1664-8021

ABSTRACT=<p><italic>RRM2B</italic> plays a crucial role in DNA replication, repair and oxidative stress. While germline <italic>RRM2B</italic> mutations have been implicated in mitochondrial disorders, its relevance to cancer has not been established. Here, using TCGA studies, we investigated <italic>RRM2B</italic> alterations in cancer. We found that <italic>RRM2B</italic> is highly amplified in multiple tumor types, particularly in <italic>MYC</italic>-amplified tumors, and is associated with increased <italic>RRM2B</italic> mRNA expression. We also observed that the chromosomal region 8q22.3–8q24, is amplified in multiple tumors, and includes <italic>RRM2B</italic>, <italic>MYC</italic> along with several other cancer-associated genes. An analysis of genes within this 8q-amplicon showed that cancers that have both <italic>RRM2B</italic>-amplified along with <italic>MYC</italic> have a distinct pattern of amplification compared to cancers that are unaltered or those that have amplifications in <italic>RRM2B</italic> or <italic>MYC</italic> only. Investigation of curated biological interactions revealed that gene products of the amplified 8q22.3–8q24 region have important roles in DNA repair, DNA damage response, oxygen sensing, and apoptosis pathways and interact functionally. Notably, <italic>RRM2B</italic>-amplified cancers are characterized by mutation signatures of defective DNA repair and oxidative stress, and at least <italic>RRM2B</italic>-amplified breast cancers are associated with poor clinical outcome. These data suggest alterations in RR2MB and possibly the interacting 8q-proteins could have a profound effect on regulatory pathways such as DNA repair and cellular survival, highlighting therapeutic opportunities in these cancers.</p>