Abstract
Objective: To analyse germ line and acquired somatic mutations of 30 high frequency genes and explore their clinical significance in hematologic malignancies. Methods: A total of 254 patients with hematologic diseases (145 males and 109 females) from Jan 2017 to Apr 2018 in the Southwest China were included and the samples from bone marrow and oral mucosa were collected, and the gene mutations of germ line and acquired somatic cells were examined by the next-generation sequencing technology or PCR. The frequency and locus of germ line and acquired somatic mutations of 30 high frequency genes, as well as their clinical significance to the diagnosis and classification in hematologic diseases were analysed. Results: 1.The frequency and locus of germ line and acquired somatic mutations, and their clinical significance: no mutation was detected in 24 cases (9.4%), and a total of 659 genetic locus mutations were detected in 230 cases (90.6%), including 520 somatic cell mutations (78.9%) and 139 germ line mutations (21.1%). The results of gene mutations are listed in order: the number of acquired somatic mutation: the number of germ line mutation: common mutation locus: the type of hematological disease for the patients diagnosed in the West China hospital, as described in Table 1. 2.Characteristics of acquired somatic and germ line mutations: the genes of WT1, U2AF1, TP53, TET2, STAG2, RUNX1, PIGA, NRAS, KIT, IDH2, EZH2, DNMT3A, CBL and BCOR were dominated by acquired somatic mutations, while the genes of ZRSR2, JAK2 and BCORL1 were dominated by germ line mutations, the genes of SRSF2, SF3B1, SETBP1, PTPN11, NPM1, PHF6, KRAS, IDH1, FLT3-ITD, ETV6 and CEBPA were detected only in acquired somatic mutations, BCOR and ASXL1 have a similar proportion of acquired somatic and germ line mutation; only 42-4C>A of ZRSR2 mutation was existed in both somatic and germ line, however, the mutation sites of the acquired somatic and germ line of other genes have not been found to be existed at the same time. 3.The clinical significance of the acquired somatic and germ line mutation: It was found that the genes of TP53, SF3B1, EZH2 and DNMT3A tend to appear in MDS, the genes of ZRSR2, WT1, U2AF1, TET2, RUNX1, NRAS, NPM1, KRAS, KIT, IDH1/2, FLT3-ITD, CEBPA and BCOR tend to appear in AML, and the similar probability of the STAG2, PTPN11, PHF6, ETV6, CBL, BCORL1, ASXL1 and NF1 genes appear in AML and MDS, while the genes of PIGA tend to appear in PNH, and BCOR in AA. Conclusion: The acquired somatic and germ line mutations are significantly different in the frequency, mutation site and the type of hematological disease, and the further research will clarify their potential roles in the pathogenesis of hematological tumors, and have important clinical significance for the classification and prognosis of the hematological diseases.
Key words: gene mutation, somatic, germ line, hematologic malignancies
No relevant conflicts of interest to declare.
