Analysis of Pathogenic and Cancer-Driver Mutations in the Growth Hormone Receptor Gene
Start Date
April 2024
Location
MCD 134
Abstract
The growth hormone receptor (GHR) gene codes for a protein that is important in the growth hormone pathway and in multiple growth regulation pathways. As people age, they proceed to replicate their cells, but there are more risk factors for mutations in the genome. When mutations occur in the gene for this receptor, expression of GH is altered in a way that alters growth factors and cellular replication. We hypothesize that if mutations occur in the conserved domains of GHR, they will disrupt functionality of the protein and be more pathogenic. This study aimed to identify mutations of the GHR gene based on several factors and determine their overall pathogenicity in regards to cancer. This was done by collecting data from the Catalogue of Somatic Mutations in Cancer (COSMIC), analyzing the data based on age, histology, and mutation type, and running the data using Cancer-Related Analysis of Variants Toolkit (CRAVAT) software to determine whether these mutations are cancer drivers. We also plan to simulate molecular models of dysfunctional proteins and match the disruptive mutations with the ages to see if there are differences which are associated with accelerated aging and cancer. GHR mutations were most common in skin, haematopoietic and lymphoid tissue, and prostates as missense substitutions. They most often present as carcinomas and are greatest in incidence in the age groups 51-60, 61-70, and 71-80. As well as this, the mutations in the conserved region of the GHR gene that were associated with cancer were significantly greater than those of the non conserved regions based on chi-squared analysis. Several pathogenic mutations were found to disrupt function of GHR and thus be cancer drivers in this study.
Analysis of Pathogenic and Cancer-Driver Mutations in the Growth Hormone Receptor Gene
MCD 134
The growth hormone receptor (GHR) gene codes for a protein that is important in the growth hormone pathway and in multiple growth regulation pathways. As people age, they proceed to replicate their cells, but there are more risk factors for mutations in the genome. When mutations occur in the gene for this receptor, expression of GH is altered in a way that alters growth factors and cellular replication. We hypothesize that if mutations occur in the conserved domains of GHR, they will disrupt functionality of the protein and be more pathogenic. This study aimed to identify mutations of the GHR gene based on several factors and determine their overall pathogenicity in regards to cancer. This was done by collecting data from the Catalogue of Somatic Mutations in Cancer (COSMIC), analyzing the data based on age, histology, and mutation type, and running the data using Cancer-Related Analysis of Variants Toolkit (CRAVAT) software to determine whether these mutations are cancer drivers. We also plan to simulate molecular models of dysfunctional proteins and match the disruptive mutations with the ages to see if there are differences which are associated with accelerated aging and cancer. GHR mutations were most common in skin, haematopoietic and lymphoid tissue, and prostates as missense substitutions. They most often present as carcinomas and are greatest in incidence in the age groups 51-60, 61-70, and 71-80. As well as this, the mutations in the conserved region of the GHR gene that were associated with cancer were significantly greater than those of the non conserved regions based on chi-squared analysis. Several pathogenic mutations were found to disrupt function of GHR and thus be cancer drivers in this study.
