Translational Oncology (Jul 2020)
Comprehensive Characterization of the Mutational Landscape in Localized Anal Squamous Cell Carcinoma
- Lucía Trilla-Fuertes,
- Ismael Ghanem,
- Joan Maurel,
- Laura G-Pastrián,
- Marta Mendiola,
- Cristina Peña,
- Rocío López-Vacas,
- Guillermo Prado-Vázquez,
- Elena López-Camacho,
- Andrea Zapater-Moros,
- Victoria Heredia,
- Miriam Cuatrecasas,
- Pilar García-Alfonso,
- Jaume Capdevila,
- Carles Conill,
- Rocío García-Carbonero,
- Karen E. Heath,
- Ricardo Ramos-Ruiz,
- Carlos Llorens,
- Ángel Campos-Barros,
- Angelo Gámez-Pozo,
- Jaime Feliu,
- Juan Ángel Fresno Vara
Affiliations
- Lucía Trilla-Fuertes
- Biomedica Molecular Medicine SL, C/Faraday 7, 28049, Madrid, Spain
- Ismael Ghanem
- Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain
- Joan Maurel
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Carrer de Villarroel 170, 08036, Barcelona, Spain
- Laura G-Pastrián
- Pathology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain; Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Marta Mendiola
- Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain; Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Av. Monforte de Lemos 5, 28029, Madrid, Spain
- Cristina Peña
- Pathology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain
- Rocío López-Vacas
- Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Guillermo Prado-Vázquez
- Biomedica Molecular Medicine SL, C/Faraday 7, 28049, Madrid, Spain
- Elena López-Camacho
- Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Andrea Zapater-Moros
- Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Victoria Heredia
- Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Av. Monforte de Lemos 5, 28029, Madrid, Spain; Translational Oncology Lab, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Miriam Cuatrecasas
- Pathology Department, Hospital Clínic Universitari de Barcelona, Carrer de Villarroel 170, 08036, Barcelona, Spain
- Pilar García-Alfonso
- Medical Oncology Department, Hospital General Universitario Gregorio Marañón, C/ Dr Esquerdo 46, 28007, Madrid, Spain
- Jaume Capdevila
- Medical Oncology Service, Vall Hebron University Hospital. Vall Hebron Institute of Oncology (VHIO), Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain
- Carles Conill
- Radiotherapy Oncology Department, Hospital Clínic Universitari de Barcelona, Carrer de Villarroel 170, 08036, Barcelona, Spain
- Rocío García-Carbonero
- Medical Oncology Department, Hospital Universitario 12 de Ocubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Av. Córdoba s/n, 28041, Madrid, Spain
- Karen E. Heath
- Institute of Medical and Molecular Genetics, IdiPAZ, Hospital Universitario La Paz /& CIBERER, Unit 753, ISCIII, Paseo de la Castellana 261, 28046, Madrid, Spain
- Ricardo Ramos-Ruiz
- Genomics Unit Cantoblanco, Parque Científico de Madrid, C/ Faraday 7, 28049, Madrid, Spain
- Carlos Llorens
- Biotechvana SL, Parque Científico de Madrid, C/ Faraday 7, 28049, Madrid, Spain
- Ángel Campos-Barros
- Institute of Medical and Molecular Genetics, IdiPAZ, Hospital Universitario La Paz /& CIBERER, Unit 753, ISCIII, Paseo de la Castellana 261, 28046, Madrid, Spain
- Angelo Gámez-Pozo
- Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain
- Jaime Feliu
- Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain; Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Av. Monforte de Lemos 5, 28029, Madrid, Spain; Cátedra UAM-Amgen, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain; Address all correspondence to: Jaime Feliu, Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain. or Juan Ángel Fresno Vara, Molecular Oncology & Pathology Lab, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain.
- Juan Ángel Fresno Vara
- Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Av. Monforte de Lemos 5, 28029, Madrid, Spain; Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain; Address all correspondence to: Jaime Feliu, Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain. or Juan Ángel Fresno Vara, Molecular Oncology & Pathology Lab, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain.
- Journal volume & issue
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Vol. 13,
no. 7
p. 100778
Abstract
Anal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemoradiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary. We analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high-impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variants and prognosis was also studied. The list of high-impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants in BRCA2, ZNF750, FAM208B, ZNF599, and ZC3H13 genes are related with poor disease-free survival in ASCC. This may help to stratify the patient's prognosis and open new avenues for potential therapeutic intervention. In conclusion, sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.
