Deep sequencing reveals the molecular pathology characteristics between primary uterine leiomyoma and pulmonary benign metastasizing leiomyoma
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Pulmonary benign metastasizing leiomyoma (PBML), a rare condition of smooth muscle tumor, originates from women with a history of uterine leiomyoma (LM). Numerous genetic studies of uterine LM have been reported; however, there are few cytogenetic and molecular descriptions of PBML. Therefore, molecular subtyping is necessary to understand the pathogenesis of metastasizing sites.
Driver gene exon-capture sequencing was performed on one patient’s peripheral blood, paraffin samples from primary uterine LM, and lung metastasizing leiomyoma 8 years later.
The results showed that the same missense mutations of BLMH, LRP2, MED12, SMAD2, and UGT1A8 were concurrently mutated in the primary uterine LM and the PBML. Moreover, a splice mutation of PTEN (c.492+1G>A) was uniquely identified in the lung metastasis of the patient.
This study indicates that the metastatic lung lesions were derived from the same malignant cell clone of uterine LMs and later acquired the novel driver mutations in the evolution of the tumor. In addition, driver gene sequencing can discriminate somatic driver mutations as biological indicators of potential malignant leiomyoma and can identify pathogenic variation driver mutations, which could be used for individualized therapy.
KeywordsBenign metastasizing leiomyoma Uterine leiomyoma Driver gene Targeted deep sequencing
Pulmonary benign metastasizing leiomyoma
Chest computed tomography
Somatic single nucleotide variations
Insertions or deletion
Benign metastasizing leiomyoma
Mediator subcomplex 12
We would like to thank Dr. Lianpeng Chang for his contribution in data analysis. The present study was supported by the Science Technology Department of Zhejiang Province (Grant number 2016C33116), the National Natural Science Fundation of China (Grant numbers 81772575, 81502463), the CSCO Merck Serono Oncology Research Fund, SCORE (Grant number Y-MX2015-038), the Natural Science Foundation of Zhejiang Province (Grant numbers LY15H160053, LQ15H070004) and the Key Research Project of Science Technology Department of Zhejiang Province (Grant number 2015C03030).
Compliance with ethical standards
Conflict of interest
No potential conflicts of interest were disclosed.
The project was approved by the Ethics Committees of Zhejiang Provincial People’s Hospital.
Written informed consent was obtained from the patient and her respective family.
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