DOI: 10.57760/sciencedb.j00217.00320
title: Association of Unique SAMHD1 mutations with selected solid tumors
title: SAMHD1突变与实体瘤的相关性

description: OBJECTIVE Application of TCGA database information to explore the correlation between SAMHD1 mutations and solid tumor.METHODS The mutation rates of SAMHD1 in 12 solid tumors were compared by TCGA and COSMIC database information.16 mammalian SAMHD1 sequences were downloaded from NCBI and UCSC for comparison, the conserved amino acid sites were screened, and the mutation sites were analyzed. Three different calculation tools (PROVEAN、SIFT、PolyPhen2) were used to calculate the mutation properties. The X-ray structure of SAMHD1 was downloaded from PDB database to explore the effect of mutation site on the maintenance of crystal tetramer structure. The expression pattern of SAMHD1 in gastric cancer was explored by qRT-PCR, and the correlation between SAMHD1 expression and clinicopathological features was analyzed.RESULTS SAMHD1 has a high mutation rate in most solid tumors. Most of the mutations were non-synonymous, and the majority were located in the dNTPase-containing HD domain of SAMHD1.The majority of the tumor-associated mutations were found in conserved amino acids in mammalian SAMHD1, and many are expected to affect the protein’s function. These nonsynonymous mutations of SAMHD1 also affect the formation and maintenance of its crystal tetramer. The expression levels of SAMHD1in gastric cancer was statistically signiﬁcant lower, and the down-regulation of SAMHD1 is associated with adverse histological classification.CONCLUSION These observations suggest that SAMHD1 has a suppressive effect on the development and/or maintenance of certain solid tumors and may represent a potential target for cancer therapeutics.
description: OBJECTIVE Application of TCGA database information to explore the correlation between SAMHD1 mutations and solid tumor.METHODS The mutation rates of SAMHD1 in 12 solid tumors were compared by TCGA and COSMIC database information.16 mammalian SAMHD1 sequences were downloaded from NCBI and UCSC for comparison, the conserved amino acid sites were screened, and the mutation sites were analyzed. Three different calculation tools (PROVEAN、SIFT、PolyPhen2) were used to calculate the mutation properties. The X-ray structure of SAMHD1 was downloaded from PDB database to explore the effect of mutation site on the maintenance of crystal tetramer structure. The expression pattern of SAMHD1 in gastric cancer was explored by qRT-PCR, and the correlation between SAMHD1 expression and clinicopathological features was analyzed.RESULTS SAMHD1 has a high mutation rate in most solid tumors. Most of the mutations were non-synonymous, and the majority were located in the dNTPase-containing HD domain of SAMHD1.The majority of the tumor-associated mutations were found in conserved amino acids in mammalian SAMHD1, and many are expected to affect the protein’s function. These nonsynonymous mutations of SAMHD1 also affect the formation and maintenance of its crystal tetramer. The expression levels of SAMHD1in gastric cancer was statistically signiﬁcant lower, and the down-regulation of SAMHD1 is associated with adverse histological classification.CONCLUSION These observations suggest that SAMHD1 has a suppressive effect on the development and/or maintenance of certain solid tumors and may represent a potential target for cancer therapeutics.