Evolution of retrovirus-infected premalignant T-cell clones prior to Adult T-cell leukemia/lymphoma diagnosis
| Autor: | Aviva Witkover, Charles R. M. Bangham, Nicolas Gillet, Lucy Cook, Liew Jun Mun, Aileen G. Rowan, Anat Melamed, Paul Fields, Graham P. Taylor, Maria-Antonietta Demontis, Richard Dillon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
viruses T-Lymphocytes medicine.disease_cause LYMPHOCYTES Biochemistry DISEASE 0302 clinical medicine immune system diseases hemic and lymphatic diseases LEUKEMIA-LYMPHOMA Leukemia-Lymphoma Adult T-Cell Longitudinal Studies 1102 Cardiorespiratory Medicine and Haematology RISK Mutation Human T-lymphotropic virus 1 Hematology biology MONOCLONAL PROLIFERATION CANCER Leukemia 030220 oncology & carcinogenesis SURVIVAL Clone (B-cell biology) Life Sciences & Biomedicine HTLV-1 CARRIERS medicine.medical_specialty LONG-TERM Immunology Adult T-cell leukemia/lymphoma Evolution Molecular 03 medical and health sciences Internal medicine medicine Humans Science & Technology business.industry Cancer 1103 Clinical Sciences Cell Biology SOMATIC MUTATIONS medicine.disease biology.organism_classification HTLV-I Infections United Kingdom Lymphoma Clone Cells 030104 developmental biology Cancer research Leukocytes Mononuclear 1114 Paediatrics and Reproductive Medicine business |
| Popis: | Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1–infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1–infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|