Effect of germline polymorphisms on somatic mutations in High Grade Serous ovarian cancer
Start Date
8-11-2017 1:30 PM
End Date
8-11-2017 5:30 PM
Abstract
Abstract: Ovarian cancer ranks fifth in cancer related deaths among gynecological cancers. A woman's risk of getting ovarian cancer during her lifetime is about 1 in 75. Her lifetime chance of dying from ovarian cancer is about 1 in 100. High-grade serous carcinoma is the most aggressive type of ovarian cancer accounting for up to 70% of the cases and is associated with late detection and poor outcomes. Currently, the treatment modalities available fail to enhance the 5 year survival rate of the patient. Consequently, there is no effective treatment modality that can specifically target ovarian cancer to increase the lifespan and quality of life of the patient. The protein p53 has many anti-cancer functions and hence is referred to as a tumor suppressor or the guardian of the genome. This protein p53 is dysfunctional in cancer, including over 96% of High-grade serous ovarian cancer (HGSOC). As a result, the protein has altered wild-type p53 activity and is said to have gone rogue due to abnormal function. In human populations, codon 72 of p53 has either the sequence CCC, which encodes amino acid proline, or CGC, which encodes amino acid arginine. This sequence variation is called a germline polymorphism. The germline polymorphism results in a structural change of p53 giving rise to variants of distinct properties. Comparative sequence analyses in non-human primates suggested that the p53-P72 is the ancestral form (present in African and Asian populations), although p53-R72 occurs at a high frequency (>50%) in populations that live away from the equator (Caucasian populations). This polymorphism occurs in a region of p53, which is known to be important for the anti-cancer functions of this protein. Hence we are trying to elucidate the role that the p53 codon 72 polymorphism that is common as a germline mutation across geographical and ethnic populations could play in manipulating the effect of somatic mutations in p53 thus affecting cancer progression.
Effect of germline polymorphisms on somatic mutations in High Grade Serous ovarian cancer
Abstract: Ovarian cancer ranks fifth in cancer related deaths among gynecological cancers. A woman's risk of getting ovarian cancer during her lifetime is about 1 in 75. Her lifetime chance of dying from ovarian cancer is about 1 in 100. High-grade serous carcinoma is the most aggressive type of ovarian cancer accounting for up to 70% of the cases and is associated with late detection and poor outcomes. Currently, the treatment modalities available fail to enhance the 5 year survival rate of the patient. Consequently, there is no effective treatment modality that can specifically target ovarian cancer to increase the lifespan and quality of life of the patient. The protein p53 has many anti-cancer functions and hence is referred to as a tumor suppressor or the guardian of the genome. This protein p53 is dysfunctional in cancer, including over 96% of High-grade serous ovarian cancer (HGSOC). As a result, the protein has altered wild-type p53 activity and is said to have gone rogue due to abnormal function. In human populations, codon 72 of p53 has either the sequence CCC, which encodes amino acid proline, or CGC, which encodes amino acid arginine. This sequence variation is called a germline polymorphism. The germline polymorphism results in a structural change of p53 giving rise to variants of distinct properties. Comparative sequence analyses in non-human primates suggested that the p53-P72 is the ancestral form (present in African and Asian populations), although p53-R72 occurs at a high frequency (>50%) in populations that live away from the equator (Caucasian populations). This polymorphism occurs in a region of p53, which is known to be important for the anti-cancer functions of this protein. Hence we are trying to elucidate the role that the p53 codon 72 polymorphism that is common as a germline mutation across geographical and ethnic populations could play in manipulating the effect of somatic mutations in p53 thus affecting cancer progression.
