Dataset Information

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

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.

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.

SUBMITTER: Huang J

PROVIDER: S-EPMC9482747 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

Huang Jiannan J Xu Wenshuai W Liu Peng P Liu Yaping Y Shen Cheng C Liu Song S Wang Yani Y Wang Jun J Zhang Tengyue T He Yudi Y Cheng Chongsheng C Yang Luning L Zhang Weihong W Tian Xinlun X Xu Kai-Feng KF

BMC pulmonary medicine 20220918 1

<h4>Background</h4>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.<h4>Methods</h4>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-dr ...[more]

PMID: 36117164

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Dataset Information

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

Background

Methods

Results

Conclusions

Publications

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

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