Abstract
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis. Eighty-three percent of mutations detected in tumors were also observed in cell-free DNAs. During the disease course, mutations were detectable in cell-free DNAs in a refractory case, while they disappeared in a chemosensitive case. These data suggest that the disease-specific gene mutations serve as sensitive indicators for ctDNAs and may also be applicable for non-invasive monitoring of minimal residual diseases in AITL.
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Acknowledgments
This work was supported by Grants-in-Aid for Scientific Research (KAKENHI: 16H02660 to S.C.; JP16K15497 to M.S.-Y.) from the Ministry of Education, Culture, Sports, and Science of Japan and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development, AMED. This work was also supported by research grants from the Daiichi Sankyo Foundation of Life Science to M.S.-Y. and The Uehara Memorial Foundation to S.C.
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M.S.-Y., R.N.-M., D.K., and S.C. designed and performed research, analyzed data, and wrote the paper; K.H., T.N., T.K., N.K., Y.Y., N.O., Y.H., and A.S. contributed to the sample collection and attended the vital discussion.
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Sakata-Yanagimoto, M., Nakamoto-Matsubara, R., Komori, D. et al. Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma. Ann Hematol 96, 1471–1475 (2017). https://doi.org/10.1007/s00277-017-3038-2
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DOI: https://doi.org/10.1007/s00277-017-3038-2