Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan
Affiliations: [a] Department of Histopathology and Morbid Anatomy, University of Health Sciences, Lahore, Pakistan | [b] Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan | [c] Department of Obstetrics and Gynecology, Jinnah Hospital, Lahore, Pakistan | [d] Department of Oncology, INMOL Hospital, Lahore, Pakistan
Correspondence:
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Corresponding author: Saba Khaliq, Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan. E-mail: [email protected].
Abstract: BACKGROUND: Genetic mutations, peritoneal metastasis and frequent development of chemoresistance worsen the prognosis of ovarian carcinoma. OBJECTIVE: The objective of the study is to determine mutations in cancer susceptibility genes in relation with chemotherapy response. METHODS: In this follow up descriptive study, 47 consenting female patients diagnosed with surface epithelial ovarian cancer were observed for six months after completion of chemotherapy to see the treatment response. For genetic analysis, the DNA extraction was done and the genomic regions of different exons of BRCA1/2, PALB2, CHEK2, BAP1, CTNNB1, HOXB13, and PIK3CA were amplified using gene specific primers followed by Sanger Sequencing. RESULTS: 86.7% of the patients were sensitive to chemotherapy whereas 13.3% showed resistance. Genetic variants of BRCA1 in 7%, BRCA2 in 4.7%, PIK3CA in 9.3%, PALB2 in 7%, CHEK2 in 2.3%, BAP1 in 2.3%, and CTNNB1 in 2.3% of the patients were found. There was also a significant association between TNM stage and the treatment response (p< 0.01). Of the patients with no mutations, 90.9% showed chemosensitivity as opposed to 70% in mutations group. CONCLUSION: Our study exhibits the pivotal role of genetic analysis in predicting the treatment response and paving pathway for patient tailored targeted therapy in Pakistani population.
