A research team led by Prof. WANG Yuexiang from the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences discovered a novel oncogenic driver gene in human lung cancer, the leading cause of cancer-related mortality worldwide.
Their findings were published in Journal of Experimental Medicine on June 18.
Approximately 85% of all lung cancer cases are non-small cell lung cancers (NSCLCs). Although tyrosine kinase inhibitors and immunotherapy have contributed to survival benefits in some patients, the overall survival rates for NSCLCs remain low.
Patients with NSCLC that are driven by KRAS mutations are often unresponsive to tyrosine kinase inhibitors and have a poor prognosis. Although inhibitors for the KRASG12C mutant have been approved to treat NSCLC patients, a general strategy that targets all KRAS mutants remains elusive.
Central precocious puberty (CPP) is largely caused by germline mutations in the MKRN3 gene. Interestingly, CPP has been epidemiologically linked to various diseases in adulthood, including cancers. Cohorts of individuals with CPP show an increased risk of malignancies such as lung cancers.
To investigate whether central precocious puberty-associated MKRN3 gene is mutated in human cancers, the research team led by Prof. WANG Yuexiang queried The Cancer Genome Atlas (TCGA) Pan-Cancer genomic data sets. Strikingly, MKRN3 is frequently mutated in NSCLCs. MKRN3 aberrations are significantly enriched in human NSCLC samples harboring oncogenic KRAS mutations.
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Journal of Experimental Medicine: Research Paper:
