Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple genetic alterations. To determine the frequency of common genetic mutations and possible prognostic markers in childhood T-ALL, we performed targeted sequencing of 67 genes across 64 cases treated accordin...

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Autores principales:	Ya-Hsuan Chang, Chih-Hsiang Yu, Shiann-Tarng Jou, Chien-Yu Lin, Kai-Hsin Lin, Meng-Yao Lu, Kang-Hsi Wu, Hsiu-Hao Chang, Dong-Tsamn Lin, Shu-Wha Lin, Hsuan-Yu Chen, Yung-Li Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6c4e6d2f9484ac082b1174d324876c5
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spelling	oai:doaj.org-article:d6c4e6d2f9484ac082b1174d324876c52021-12-02T14:12:45ZTargeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia10.1038/s41598-020-80613-62045-2322https://doaj.org/article/d6c4e6d2f9484ac082b1174d324876c52021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80613-6https://doaj.org/toc/2045-2322Abstract T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple genetic alterations. To determine the frequency of common genetic mutations and possible prognostic markers in childhood T-ALL, we performed targeted sequencing of 67 genes across 64 cases treated according to Taiwan Pediatric Oncology Group protocols between January 2002 and December 2015. Together, 302 variants were identified in 60 genes including 233 single nucleotide variants and 69 indels. Sixty-four samples had a median number of six genetic lesions each (range 1–17). Thirteen genes had mutation frequencies > 10%, and 5 were > 20%, with the highest being NOTCH1 (70.31%). Protocadherins FAT1 (32.81%) and FAT3 (17.19%), and the ubiquitin ligase component FBXW7 (28.13%) had higher mutation frequencies than previously reported. Other mutation frequencies (PHF6, DNM2, DNMT3A, CNOT3, and WT1) were within previously reported ranges. Three epigenetic-related genes (KMT2D, DNMT3A, and EZH2) were mutated in our cohort. JAK-STAT signaling pathway genes had mutation frequencies of 3–13% and were observed in 23 cases (35.94%). Changes to genes in the ErbB signaling pathway were detected in 20 cases (31.25%). Patients with NOTCH1/FBXW7 mutations and RAS/PTEN germline exhibited better 5-year overall survival rates.Ya-Hsuan ChangChih-Hsiang YuShiann-Tarng JouChien-Yu LinKai-Hsin LinMeng-Yao LuKang-Hsi WuHsiu-Hao ChangDong-Tsamn LinShu-Wha LinHsuan-Yu ChenYung-Li YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ya-Hsuan Chang Chih-Hsiang Yu Shiann-Tarng Jou Chien-Yu Lin Kai-Hsin Lin Meng-Yao Lu Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Hsuan-Yu Chen Yung-Li Yang Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
description	Abstract T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple genetic alterations. To determine the frequency of common genetic mutations and possible prognostic markers in childhood T-ALL, we performed targeted sequencing of 67 genes across 64 cases treated according to Taiwan Pediatric Oncology Group protocols between January 2002 and December 2015. Together, 302 variants were identified in 60 genes including 233 single nucleotide variants and 69 indels. Sixty-four samples had a median number of six genetic lesions each (range 1–17). Thirteen genes had mutation frequencies > 10%, and 5 were > 20%, with the highest being NOTCH1 (70.31%). Protocadherins FAT1 (32.81%) and FAT3 (17.19%), and the ubiquitin ligase component FBXW7 (28.13%) had higher mutation frequencies than previously reported. Other mutation frequencies (PHF6, DNM2, DNMT3A, CNOT3, and WT1) were within previously reported ranges. Three epigenetic-related genes (KMT2D, DNMT3A, and EZH2) were mutated in our cohort. JAK-STAT signaling pathway genes had mutation frequencies of 3–13% and were observed in 23 cases (35.94%). Changes to genes in the ErbB signaling pathway were detected in 20 cases (31.25%). Patients with NOTCH1/FBXW7 mutations and RAS/PTEN germline exhibited better 5-year overall survival rates.
format	article
author	Ya-Hsuan Chang Chih-Hsiang Yu Shiann-Tarng Jou Chien-Yu Lin Kai-Hsin Lin Meng-Yao Lu Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Hsuan-Yu Chen Yung-Li Yang
author_facet	Ya-Hsuan Chang Chih-Hsiang Yu Shiann-Tarng Jou Chien-Yu Lin Kai-Hsin Lin Meng-Yao Lu Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Hsuan-Yu Chen Yung-Li Yang
author_sort	Ya-Hsuan Chang
title	Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
title_short	Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
title_full	Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
title_fullStr	Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
title_full_unstemmed	Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia
title_sort	targeted sequencing to identify genetic alterations and prognostic markers in pediatric t-cell acute lymphoblastic leukemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d6c4e6d2f9484ac082b1174d324876c5
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Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia

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