Dynamic Evolution of Clonal Composition and Neoantigen Landscape in Recurrent Metastatic Melanoma with a Rare Combination of Driver Mutations
| العنوان: | Dynamic Evolution of Clonal Composition and Neoantigen Landscape in Recurrent Metastatic Melanoma with a Rare Combination of Driver Mutations |
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| المؤلفون: | Dan Lipsker, Guillaume Davidson, Gabriel G. Malouf, Marie Ennen, Irwin Davidson, Alice Kieny, Sebastien Coassolo, Erwan Pencreach |
| المساهمون: | Department of Functional Genomics and Cancer [Illkirch], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), CHU Strasbourg, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC) |
| المصدر: | Journal of Investigative Dermatology Journal of Investigative Dermatology, Nature Publishing Group, 2019, 139 (8), pp.1769-1778.e2. ⟨10.1016/j.jid.2019.01.027⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Proto-Oncogene Proteins B-raf, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Genome instability, Skin Neoplasms, Oncogene Proteins, Fusion, Carcinogenesis, Biopsy, DNA Mutational Analysis, MAP Kinase Kinase 1, Mutation, Missense, A Kinase Anchor Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biology, medicine.disease_cause, Biochemistry, Somatic evolution in cancer, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, Exome Sequencing, medicine, Humans, Missense mutation, Melanoma, Molecular Biology, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Skin, Chromosome 7 (human), Mutation, Cell Biology, medicine.disease, Cytoskeletal Proteins, HEK293 Cells, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Neoplasm Recurrence, Local |
| الوصف: | In melanoma, initiating oncogenic mutations in BRAF or NRAS are detected in premalignant lesions that accumulate additional mutations and genomic instability as the tumor evolves to the metastatic state. Here we investigate evolution of clonal composition and neoantigen landscape in an atypical melanoma displaying recurrent cutaneous lesions over a 6-year period without development of extracutaneous metastases. Whole exome sequencing of four cutaneous lesions taken during the 6-year period identified a collection of single nucleotide variants and small insertions and deletions shared among all tumors, along with progressive selection of subclones displaying fewer single nucleotide variants. Later tumors also displayed lower neoantigen burden compared to early tumors, suggesting that clonal evolution was driven, at least in part, by counter selection of subclones with high neoantigen burdens. Among the selected mutations are a missense mutation in MAP2K1 (F53Y) and an inversion on chromosome 7 generating a AKAP9-BRAF fusion. The mutant proteins cooperatively activate the MAPK signaling pathway confirming they are potential driver mutations of this tumor. We therefore describe the long-term genetic evolution of cutaneous metastatic melanoma characterized by an unexpected phenotypic stability and neoantigen-driven clonal selection. |
| اللغة: | English |
| تدمد: | 0022-202X 1523-1747 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0248ec183f5db204434d7549a87bdb8Test https://hal.archives-ouvertes.fr/hal-02386454Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c0248ec183f5db204434d7549a87bdb8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0022202X 15231747 |
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