title: Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical care.
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.
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.|Inserm U1079, Rouen, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Muller
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Brault
authors.affiliation: Recombination and Genetic Instability, UMR 3244, Institut Curie, Paris, France.
authors.forename: Allyson
authors.initials: A
authors.lastname: Holmes
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.
authors.forename: Angelina
authors.initials: A
authors.lastname: Legros
authors.affiliation: Biopathology Department, Institut Curie, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jeannot
authors.affiliation: Department of Radiotherapy, Institut Curie, Paris, France.
authors.forename: Maura
authors.initials: M
authors.lastname: Campitelli
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Rousselin
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goardon
authors.affiliation: Inserm U1079, Rouen, France.|Department of Genetics, University Hospital, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.|Inserm U1079, Rouen, France.|Caen University, Caen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Krieger
authors.affiliation: Gynecology Oncology Department, CCC François Baclesse, Caen, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Crouet
authors.affiliation: Recombination and Genetic Instability, UMR 3244, Institut Curie, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Biopathology Department, Institut Curie, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.|Inserm U1079, Rouen, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vaur
authors.affiliation: Department of Cancer Biology and Genetics, CCC François Baclesse, Caen, France.|Inserm U1079, Rouen, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Castéra
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D018797:Cell Cycle Proteins / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D052138:Genes, Neoplasm; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D057285:Precision Medicine / Q000639:trends*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D044767:Ubiquitin-Protein Ligases; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cervix; NGS; diagnosis; panel; targeted therapie