Large-scale analysis of KMT2 mutations defines a distinctive molecular subset with treatment implication in gastric cancer

• Published in: Oncogene 2021-07, Vol.40 (30), p.4894-4905
• Main Authors: Wang, Jingyuan, Xiu, Joanne, Baca, Yasmine, Battaglin, Francesca, Arai, Hiroyuki, Kawanishi, Natsuko, Soni, Shivani, Zhang, Wu, Millstein, Joshua, Salhia, Bodour, Goldberg, Richard M., Philip, Philip A., Seeber, Andreas, Hwang, Jimmy J., Shields, Anthony F., Marshall, John L., Astsaturov, Igor, Craig Lockhart, A., Gatalica, Zoran, Michael Korn, W., Lenz, Heinz-Josef
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67/1504/1829; 631/67/1857; Aged; Aged, 80 and over; Apoptosis; Biomarkers, Tumor; Cancer; Care and treatment; Cell Biology; Cell cycle; Databases, Genetic; Development and progression; DNA damage; DNA Mismatch Repair; DNA Mutational Analysis; DNA repair; Drug delivery; Epigenetic inheritance; Epigenetics; Female; Gastric cancer; Gene Frequency; Gene mutations; Genetic aspects; Health aspects; Histone methyltransferase; Histone-lysine N-methyltransferase; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Human Genetics; Humans; Immunohistochemistry; Immunosuppressive agents; Internal Medicine; Isoenzymes - genetics; Kaplan-Meier Estimate; Lysine; Male; MAP kinase; Medicine; Medicine & Public Health; Metabolism; Metastases; Methyltransferase; Methyltransferases; Microenvironments; Microsatellite Instability; Middle Aged; Mutants; Mutation; Mutation rates; N-Methyltransferase; Neoplasm Grading; Neoplasm Staging; Oncology; Oncology, Experimental; Patients; PD-L1 protein; Prognosis; Solid tumors; Stomach cancer; Stomach Neoplasms - diagnosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Tumor Microenvironment; Tyrosine; α-Interferon
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-021-01840-3

Frequent mutations of genes in the histone-lysine N-methyltransferase 2 (KMT2) family members were identified in gastric cancers (GCs). Understanding how gene mutations of KMT2 family affect cancer progression and tumor immune microenvironment may provide new treatment strategies. A total of 1245 GCs were analyzed using next-generation sequencing, whole transcriptome sequencing, immunohistochemistry (Caris Life Sciences, Phoenix, AZ). The overall mutation rate of genes in the KMT2 family was 10.6%. Compared to KMT2 -wild-type GCs, genes involved in epigenetic modification, receptor tyrosine kinases/MAPK/PI3K, and DNA damage repair (DDR) pathways had higher mutation rates in KMT2 -mutant GCs ( p