Mutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM)

Autoři: Jie Liu aff001;  Weiwei Zhao aff005;  Xiaohua Ou aff006;  Zhen Zhao aff006;  Changming Hu aff006;  Mingming Sun aff006;  Feifei Liu aff006;  Junhao Deng aff006;  Weili Gu aff001;  Jiaying An aff002;  Qingling Zhang aff001;  Xiaoxian Zhang aff001;  Jiaxing Xie aff001;  Shiyue Li aff001;  Rongchang Chen aff009;  Shihui Yu aff005;  Nanshan Zhong aff001
Působiště autorů: Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China aff001;  Guangzhou Institute for Respiratory Health, Guangzhou, Guangdong, China aff002;  State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong, China aff003;  National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, China aff004;  Guangzhou KingMed Diagnostics Group Co., Ltd, Guangzhou, Guangdong, China aff005;  Clinical Genome Center, KingMed Center for Clinical Laboratory Co., Ltd, Guangzhou, Guangdong, China aff006;  KingMed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China aff007;  Guangzhou KingMed Translational Medicine Institute Co., Ltd, Guangzhou, Guangdong, China aff008;  Department of Pulmonary and Critical Care Medicine, Shenzhen People's Hospital, Shenzhen, Guangdong, China aff009;  KingMed JianShi Innovation Institute (Guangzhou) Co., Ltd, Guangzhou, Guangdong, China aff010
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226400


The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients’ clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31–42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM.

Klíčová slova:

Biopsy – Carcinogenesis – Human genetics – Mutation databases – Mutation detection – Nonsense mutation – Somatic mutation – Germline mutation


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