Start Date
April 2024
Location
MCD 208
Abstract
Chromobox 5 (CBX5) is a key factor in gene silencing in the replisome. The CBX5 protein, HP1α, binds heterochromatin in the centromeres and telomeres as a regulatory mechanism and suppressor of metastasis. Mutations in the CBX5 gene yield access to DNA for transcription at improper times. CBX5 also contributes to the repression of genes to accommodate the growth and development of cells. Using bioinformatic information retrieved from the Catalogue of Somatic Mutations in Cancer (COSMIC), we examined the types of mutations in coding and noncoding regions of the gene using Cancer-Related Analysis of Variants Toolkit (CRAVAT) software and analyzed the tissues and cancers in which those mutations were prevalent. Using mean age at time of sequencing as an additional measure, we analyzed the significance of these mutations to cancer and the process of accelerated aging. Mutations were found more frequently in the noncoding introns and untranslated regions of the gene, indicating that the mutations primarily affect the regulation of the protein rather than the structure. The mutations of CBX5 are most frequently missense substitutions and are most associated with carcinomas, with the large intestine, liver, and breast tissues being the most common primary sites for cancer in ages 61-80. An alteration in the frequency of cancer-associated CBX5 mutations was observed corresponding to age of senescence. By simulating the disruptive mutations observed from our previous statistics, we can infer a molecular model of gene dysfunction. Correlating these mutations with age will inform the importance of CBX5 in accelerated aging and cancer.
Determination and Analysis of Cancer-Driving Mutations in the Chromobox 5 Gene
MCD 208
Chromobox 5 (CBX5) is a key factor in gene silencing in the replisome. The CBX5 protein, HP1α, binds heterochromatin in the centromeres and telomeres as a regulatory mechanism and suppressor of metastasis. Mutations in the CBX5 gene yield access to DNA for transcription at improper times. CBX5 also contributes to the repression of genes to accommodate the growth and development of cells. Using bioinformatic information retrieved from the Catalogue of Somatic Mutations in Cancer (COSMIC), we examined the types of mutations in coding and noncoding regions of the gene using Cancer-Related Analysis of Variants Toolkit (CRAVAT) software and analyzed the tissues and cancers in which those mutations were prevalent. Using mean age at time of sequencing as an additional measure, we analyzed the significance of these mutations to cancer and the process of accelerated aging. Mutations were found more frequently in the noncoding introns and untranslated regions of the gene, indicating that the mutations primarily affect the regulation of the protein rather than the structure. The mutations of CBX5 are most frequently missense substitutions and are most associated with carcinomas, with the large intestine, liver, and breast tissues being the most common primary sites for cancer in ages 61-80. An alteration in the frequency of cancer-associated CBX5 mutations was observed corresponding to age of senescence. By simulating the disruptive mutations observed from our previous statistics, we can infer a molecular model of gene dysfunction. Correlating these mutations with age will inform the importance of CBX5 in accelerated aging and cancer.
