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Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.
- Source :
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BMC pulmonary medicine [BMC Pulm Med] 2022 Sep 18; Vol. 22 (1), pp. 354. Date of Electronic Publication: 2022 Sep 18. - Publication Year :
- 2022
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Abstract
- Background: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes.<br />Methods: Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations.<br />Results: 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax.<br />Conclusions: Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.<br /> (© 2022. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1471-2466
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC pulmonary medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36117164
- Full Text :
- https://doi.org/10.1186/s12890-022-02154-0