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Targeted exome sequencing profiles genetic alterations in leiomyosarcoma
Narasimhan P Agaram1, Lei Zhang1, Francois LeLoarer1
1Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Genes, Chromosomes & Cancer
|November 7, 2015
Summary
Leiomyosarcoma (LMS) is genetically complex, often losing tumor suppressor genes like TP53. Amplification of the MYOCD gene, crucial for smooth muscle, occurs in some LMS cases, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Leiomyosarcoma (LMS) is a complex sarcoma characterized by frequent chromosomal abnormalities.
- Identifying recurrent genetic alterations is crucial for understanding LMS pathogenesis and discovering therapeutic targets.
Purpose of the Study:
- To investigate genetic abnormalities in LMS using next-generation sequencing (NGS) and identify potential therapeutic targets.
- To analyze single nucleotide variants, insertions/deletions, and copy number alterations in a cohort of LMS.
Main Methods:
- Targeted exome sequencing of 230 cancer-associated genes in 35 primary soft tissue and visceral LMS.
- Analysis of sequence data for genetic alterations, with key findings validated by fluorescence in situ hybridization (FISH).
Main Results:
- Losses of tumor suppressor genes PTEN, RB1, CDH1, and TP53 were frequent. TP53 mutations occurred in 37% of cases.
- Gains involved chromosome regions 17p11.2 (MYOCD) and 15q25-26 (IGF1R). MYOCD gene amplification was observed in 20% of analyzed cases.
- Low-grade LMS lacked PTEN or TP53 alterations, unlike high-grade tumors.
Conclusions:
- LMS exhibits significant genetic complexity, with frequent loss of tumor suppressor genes.
- MYOCD amplification in a subset of LMS warrants further investigation for its role in tumor development and as a potential therapeutic target.
