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

English version

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
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226400

Souhrn

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:

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

Zdroje

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

Souhrn

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Zdroje

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