Open AccessMutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM)
Author(s) -
Jie Liu,
Weiwei Zhao,
Xiaohua Ou,
Zhen Zhao,
Changming Hu,
Mingming Sun,
Feifei Liu,
Junhao Deng,
Weili Gu,
Jiaying An,
Qingling Zhang,
Xiaoxian Zhang,
Jiaxing Xie,
Shiyue Li,
Rongchang Chen,
Shihui Yu,
Nanshan Zhong
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0226400
Subject(s) - tsc2 , tsc1 , lymphangioleiomyomatosis , mutation , genetics , medicine , tuberous sclerosis , biology , cancer research , pathology , gene , pi3k/akt/mtor pathway , signal transduction
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.