A Methodology for Assessing Tumor Clonality of Adult T Cell Leukemia/Lymphoma

Autor: Tomohiro Yamakawa, Naoki Uno, Daisuke Sasaki, Norihito Kaku, Kei Sakamoto, Kosuke Kosai, Hiroo Hasegawa, Yasushi Miyazaki, Katsunori Yanagihara
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecular Therapy: Methods & Clinical Development, Vol 19, Iss , Pp 467-473 (2020)
Druh dokumentu: article
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2020.10.015
Popis: While clonal heterogeneity has been demonstrated in most cancers, quantitative assessment of individual tumor clones has not been translated to inform clinical practice. A few methods have been developed to investigate the tumor clonality of adult T cell leukemia/lymphoma (ATLL), but currently there is no clinically translatable method available for quantifying individual tumor clones in ATLL patients. Here, we present a methodology to assess the tumor clonality of ATLL and quantify patient-specific tumor clones in a clinical setting. The methodology consists of three steps: (1) selective amplification of restriction fragments containing a human T cell leukemia virus type 1 (HTLV-1) integration site, (2) amplicon deep sequencing to estimate the clonal structure and identify HTLV-1 integration sites of dominant clones, and (3) digital PCR targeting the HTLV-1 integration sites of the dominant clones to quantify specific tumor clones. We successfully tracked individual tumor clones using this approach and demonstrated that each clone had a distinct response to therapies. The procedure is straightforward and clinically feasible, which should facilitate the proper assessment and management of ATLL.
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