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Clinical utility of target capture-based panel sequencing in hematological malignancies: A multicenter feasibility study.

ABSTRACT: Although next-generation sequencing-based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, and diffuse large B-cell lymphoma. Out of 96 eligible patients, 79 patients (82%) showed potentially actionable findings, based on the clinical sequencing assays. We identified that genetic alterations with a strong clinical significance were found at a higher frequency in terms of diagnosis (n = 60; 63%) and prognosis (n = 61; 64%) than in terms of therapy (n = 8; 8%). Three patients who harbored a germline mutation in either DDX41 (n = 2) or BRCA2 (n = 1) were provided with genetic counseling. At 6 mo after sequencing, clinical actions based on the diagnostic (n = 5) or prognostic (n = 3) findings were reported, but no patients were enrolled in a clinical trial or received targeted therapies based on the sequencing results. These results suggest that panel testing for hematological malignancies would be feasible given the availability of useful diagnostic and prognostic information. This study is registered with the UMIN Clinical Trial Registry (UMIN000029879, multiple myeloma; UMIN000031343, adult acute myeloid leukemia; UMIN000033144, diffuse large B-cell lymphoma; and UMIN000034243, childhood leukemia).

SUBMITTER: Yasuda T

PROVIDER: S-EPMC7469806 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Clinical utility of target capture-based panel sequencing in hematological malignancies: A multicenter feasibility study.

Yasuda Takahiko T Sanada Masashi M Nishijima Dai D Kanamori Takashi T Iijima Yuka Y Hattori Hiroyoshi H Saito Akiko A Miyoshi Hiroaki H Ishikawa Yuichi Y Asou Norio N Usuki Kensuke K Hirabayashi Shinsuke S Kato Motohiro M Ri Masaki M Handa Hiroshi H Ishida Tadao T Shibayama Hirohiko H Abe Masahiro M Iriyama Chisako C Karube Kennosuke K Nishikori Momoko M Ohshima Koichi K Kataoka Keisuke K Yoshida Kenichi K Shiraishi Yuichi Y Goto Hiroaki H Adachi Souichi S Kobayashi Ryoji R Kiyoi Hitoshi H Miyazaki Yasushi Y Ogawa Seishi S Kurahashi Hiroki H Yokoyama Hisayuki H Manabe Atsushi A Iida Shinsuke S Tomita Akihiro A Horibe Keizo K

Cancer science 20200717 9

Although next-generation sequencing-based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple ...[more]

PMID: 32619037

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Project description:Rubus (Rosaceae) comprises more than 500 species with additional commercially cultivated raspberries and blackberries. The most recent (> 100 years old) global taxonomic treatment of the genus defined 12 subgenera; two subgenera were subsequently described and some species were rearranged. Intra- and interspecific ploidy levels and hybridization make phylogenetic estimation of Rubus challenging. Our objectives were to estimate the phylogeny of 94 taxonomically and geographically diverse species and three cultivars using chloroplast DNA sequences and target capture of approximately 1,000 low copy nuclear genes; estimate divergence times between major Rubus clades; and examine the historical biogeography of species diversification. Target capture sequencing identified eight major groups within Rubus. Subgenus Orobatus and Subg. Anoplobatus were monophyletic, while other recognized subgenera were para- or polyphyletic. Multiple hybridization events likely occurred across the phylogeny at subgeneric levels, e.g., Subg. Rubus (blackberries) × Subg. Idaeobatus (raspberries) and Subg. Idaeobatus × Subg. Cylactis (Arctic berries) hybrids. The raspberry heritage within known cultivated blackberry hybrids was confirmed. The most recent common ancestor of the genus was most likely distributed in North America. Multiple distribution events occurred during the Miocene (about 20 Ma) from North America into Asia and Europe across the Bering land bridge and southward crossing the Panamanian Isthmus. Rubus species diversified greatly in Asia during the Miocene. Rubus taxonomy does not reflect phylogenetic relationships and subgeneric revision is warranted. The most recent common ancestor migrated from North America towards Asia, Europe, and Central and South America early in the Miocene then diversified. Ancestors of the genus Rubus may have migrated to Oceania by long distance bird dispersal. This phylogeny presents a roadmap for further Rubus systematics research. In conclusion, the target capture dataset provides high resolution between species though it also gave evidence of gene tree/species tree and cytonuclear discordance. Discordance may be due to hybridization or incomplete lineage sorting, rather than a lack of phylogenetic signal. This study illustrates the importance of using multiple phylogenetic methods when examining complex groups and the utility of software programs that estimate signal conflict within datasets.

Dataset Information

Clinical utility of target capture-based panel sequencing in hematological malignancies: A multicenter feasibility study.

Publications

Clinical utility of target capture-based panel sequencing in hematological malignancies: A multicenter feasibility study.

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