In:
BMC Pulmonary Medicine, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-09-18)
Abstract:
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. 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. 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. 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.
Type of Medium:
Online Resource
ISSN:
1471-2466
DOI:
10.1186/s12890-022-02154-0
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2059871-3
