Pan-Cancer analysis of somatic mutations in miRNA genes

Abstract

175)miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancerdriver miRNA genes. The results published here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work was supported by research grants from the Polish National Science Centre [2016/22/A/NZ2/00184 (to P.K.) and 2015/17/N/NZ3/03629 (to M.O.U-T.)] Authors contributions MUTparticipated in conceiving the study, wrote all the scripts, performed most of the computational and statistical analyses, drafted the manuscript, prepared figures, tables, and supplementary materials; PGMparticipated in conceiving the study, discussed the study on all steps of analyses, participated in manuscript preparation, performed some analyses (3D structures); PNdiscussed the analyses on all steps of the study, performed some analyses, participated in manuscript preparation; EKperformed the sequencing experiments, critically read and corrected manuscript; SSperformed the sequencing experiments, critically read and corrected manuscript; MGprovided samples for the hsa-miR-1324 and hsa-miR-142 sequencing validation experiments, advised on hematological neoplasms and head and neck cancer, critically read and corrected manuscript; PKreceived financing, participated in conceiving the study, supervised and coordinated the study, drafted the manuscript (with MUT).

Cell Division Cycle-Associated Protein 3 (CDCA3) Is a Potential Biomarker for Clinical Prognosis and Immunotherapy in Pan-Cancer

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Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen

“…Tumor associated antigens (TAAs) that serve as pan-tumor markers or targets are emerging as a key aspect of immuno-oncology. Cancer treatments may now be guided by specific targets irrespective of tumor site of origin [2,3,4,5] as opposed to single-biomarkers that are generally associated with cancer arising from a specific organ or tissue. For example, in 2017 pembrolizumab (Keytruda®) was approved for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors, making it the first cancer treatment based on a common biomarker rather than an organ or tissue-based origin [6].…”

Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

“…Tumor associated antigens (TAAs) that serve as pan-tumor markers or targets are emerging as a key aspect of immuno-oncology. Cancer treatments may now be guided by specific targets irrespective of tumor site of origin (Li et al, 2017; Looney et al, 2020; Ma et al, 2021; Urbanek-Trzeciak et al, 2020) as opposed to single-biomarkers that are generally associated with cancer arising from a specific organ or tissue. For example, in 2017 pembrolizumab (Keytruda®) was approved for patients with microsatellite instability-high (MSI-H) or mismatch repair–deficient solid tumors, making it the first cancer treatment based on a common biomarker rather than an organ or tissue-based origin (Chang et al, 2018).…”