Histone Lysine Methyltransferase KMT2C Mutation Characteristics In Breast

Background:Through incredible advancements in medical technology,personalized,precision medicine has become an important development direction for the treatment of breast cancer patients.And the application of Next Generation Sequencing(NGS)brings about a new understanding of the molecular biology of breast cancer.Some studies have shown that Histone Lysine Methyltransferase 2C(KMT2C),a relative gene of histone methyltransferase family,is an important coding gene of epigenetic modification and may be related to the occurrence and development of breast cancer.At present,the relationship between KMT2C mutation status and clinicopathological characteristics in Chinese breast cancer patients is still unclear.Objective:We explored the KMT2C gene mutation in different populations and the differences between the mutants and the non-mutants in clinicopathological characteristics,and provided a certain clinical basis for the genetic diagnosis of breast cancer and the individualized and accurate treatment.Methods:Guangdong Provincial People's Hospital(GDPH)was the setting for this retrospective study to collected the clinical characteristics of breast cancer patients and the sequencing results of KMT2C gene in primary tumor tissues detected by NGS from June 1,2017 to September 27,2018.The Chi-square test or Fisher test were performed to evaluate the correlation between the clinicopathological characteristics and KMT2C mutation of patients,and the information in TCGA and METABRIC databases were compared.Finally,the COX model was performed to evaluate the factors affecting overall survival(OS)of patients in TCGA and METABRIC databases.Significance test level a=0.05.Results:A total of 33 patients(36 mutation sites)were detected in 411 cases of breast cancer patients in our research center,the KMT2C mutation rate was 8.0%(33/411).We also detected 25 new mutation sites of KMT2C,and among the 11 cases of mutation sites reported previously,6 cases of mutation sites were first found in breast cancer.Moreover,the mutation rate of KMT2C in invasive lobular carcinoma reached 30.8%(4/13)in GDPH cohort.The TCGA and METABRIC mutation rates were 7.0%(69/981)and 14.5%(211/1454),respectively.In addition,we found that KMT2C mutations in the three groups of databases were related to the age of onset(GDPH:p=0.007;TCGA:p = 0.005;METABRIC:p=0.015),and breast cancer with HR+/HER2-type was more common(GDPH:p=0.047;TCGA:p =0.032;METABRIC:p = 0.046).The COX risk regression analysis was performed to evaluate the correlation between KMT2C mutation status and clinicopathological characteristics of patients in the TCGA and METABRIC groups.And it was found that KMT2C mutation was not a relevant risk factor for breast cancer prognosis(TCGA:HR,1.71;95%Cl,0.88-3.31;p=0.111;METABRIC:HR,2.03;95%CI,0.45-3.08;p=0.419).Conclusion:This study preliminarily elucidated KMT2C mutations in Chinese patients with breast cancer and further identified significant KMT2C mutation differences with race and ethnicity.In addition,KMT2C mutations were mainly detected in HR+/HER2-breast cancer,and it provided a theoretical basis for KMT2C as a target for cancer therapy.25 new mutation sites were found in our research center.In the future,we will conduct functional studies on newly discovered mutation sites in Chinese patients,expand the sample size,and further explore the mutation characteristics and clinical application value of KMT2C in Chinese breast cancer patients.