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Mutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM)
- Source :
- PLoS ONE, Vol 14, Iss 12, p e0226400 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Carcinogenesis
Biopsy
Science
Nonsense mutation
Gene Identification and Analysis
Surgical and Invasive Medical Procedures
Biology
Research and Analysis Methods
Germline
Database and Informatics Methods
03 medical and health sciences
Exon
0302 clinical medicine
Germline mutation
Gene duplication
Genetics
Medicine and Health Sciences
medicine
Multiplex ligation-dependent probe amplification
Indel
Mutation Detection
Multidisciplinary
Biology and Life Sciences
Human Genetics
Nonsense Mutation
Germline Mutation
medicine.disease
Biological Databases
030104 developmental biology
Oncology
030228 respiratory system
Mutation
Mutation Databases
Lymphangioleiomyomatosis
Somatic Mutation
Medicine
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....b31001089011464baff3b4607190b624