Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical careReportar como inadecuado

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* Corresponding author 1 Department of Cancer Biology and Genetics 2 Inserm U1079, Rouen 3 DIG CANCER - Dynamique de l-information génétique : bases fondamentales et cancer 4 Biopathology Department 5 Department of Radiotherapy 6 Department of genetics 7 UNICAEN - Université Caen Normandie 8 Gynecology Oncology Department

Abstract : Cancer treatment is facing major evolution since the advent of targeted therapies. Building genetic profiles could predict sensitivity or resistance to these therapies and highlight disease-specific abnormalities, supporting personalized patient care. In the context of biomedical research and clinical diagnosis, our laboratory has developed an oncogenic panel comprised of 226 genes and a dedicated bioinformatic pipeline to explore somatic mutations in cervical carcinomas, using high-throughput sequencing. Twenty-nine tumors were sequenced for exons within 226 genes. The automated pipeline used includes a database and a filtration system dedicated to identifying mutations of interest and excluding false positive and germline mutations. One-hundred and seventy-six total mutational events were found among the 29 tumors. Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA E545K, E542K and KRAS G12D, G13D and others in FBXW7 R465C, R505G, R479Q. Mutations have also been found in ALK V1149L, A1266T and EGFR T259M. These results showed that 48% of patients display at least one deleterious mutation in genes that have been already targeted by the Food and Drug Administration approved therapies. Considering deleterious mutations, 59% of patients could be eligible for clinical trials. Sequencing hundreds of genes in a clinical context has become feasible, in terms of time and cost. In the near future, such an analysis could be a part of a battery of examinations along the diagnosis and treatment of cancer, helping to detect sensitivity or resistance to targeted therapies and allow advancements towards personalized oncology.

Keywords : Cervix diagnosis NGS panel targeted therapie

Autor: Etienne Muller - Baptiste Brault - Allyson Holmes - Angelina Legros - Emmanuelle Jeannot - Maura Campitelli - Antoine Rousselin -



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