In a new comprehensive genomic study, researchers identified thousands of recurrent and protein-altering mutations in 216 malignant pleural mesothelioma (MPM) tumors. The analysis was performed using MedGenome’s OncoMD mutation database, and aims to advance personalized therapies against this rare and aggressive cancer.
The research article, “Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations,” was published in the journal Nature Genetics.
Tumors accumulate mutations as they evolve, and it is important to distinguish between non-functional mutations and functional mutations, which can alter proteins and drive molecular pathogenic events. The research team used the OncoMD database to identify some 2,700 functional (protein altering) mutations.
MDGenome’s curated knowledge database has over 1.9 million cancer mutations obtained from more than 7,000 peer-reviewed publications, annotated according to their biological relevance, drug sensitivity, and as targets in clinical discovery research. The database provides users with tools to not only identify cancer mutations, but to understand the biological role of these genetic alterations. It also constitutes the largest collection of cancer exomes, the part of the genome formed by exons, the sequences transcribed into mature RNA.
Among the results, researchers found that the genes BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 were significantly mutated in MPM. Moreover, the team found some recurrent mutations in several genes, such as SF3B1 (mutated in four of the 216 tumors) and TRAF7 (mutated in five of the 216 tumors).
“MedGenome’s OncoMD structured knowledge base can help stratify the mutations into potential drivers and passengers,” Dr. Amit Chaudhuri, vice president of Research at MedGenome and the study’s co-author, said in a press release, “Identifying driver events will enable development of targeted therapies, and where such therapies already exist, you can match the patient with the right drug. It’s the holy grail of personalized precision medicine.”
Mesothelioma is a rare but deadly cancer whose incidence has grown in the last decades, mainly due to past exposure to asbestos, one of its main risk factors. Despite efforts to discover effective therapeutic strategies against the disease and extend a patient’s life, malignant mesothelioma remains very resistant to treatments — namely, radiation and chemotherapy. According to the World Health Organization, 43,000 people worldwide die from the disease each year.
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