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Deep sequencing reveals the molecular pathology characteristics between primary uterine leiomyoma and pulmonary benign metastasizing leiomyoma

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Abbreviations

PBML:

Pulmonary benign metastasizing leiomyoma

LM:

Leiomyoma

CT:

Chest computed tomography

ER:

Estrogen receptor

PR:

Progesterone receptor

SNV:

Somatic single nucleotide variations

InDel:

Insertions or deletion

BML:

Benign metastasizing leiomyoma

MED12:

Mediator subcomplex 12

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Acknowledgements

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).

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Author notes

  1. J. Jiang and M. He are co-authors.

Authors and Affiliations

  1. Department of Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People’s Republic of China

    J. Jiang

  2. Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310014, Zhejiang, People’s Republic of China

    M. He

  3. Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Shang Tang Road 158, Hangzhou, 310014, Zhejiang, People’s Republic of China

    X. Hu, C. Ni & L. Yang

  4. Department of Thyroid and Breast Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, Zhejiang, People’s Republic of China

    C. Ni

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Correspondence to X. Hu, C. Ni or L. Yang.

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No potential conflicts of interest were disclosed.

Ethical approval

The project was approved by the Ethics Committees of Zhejiang Provincial People’s Hospital.

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Written informed consent was obtained from the patient and her respective family.

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Jiang, J., He, M., Hu, X. et al. Deep sequencing reveals the molecular pathology characteristics between primary uterine leiomyoma and pulmonary benign metastasizing leiomyoma. Clin Transl Oncol 20, 1080–1086 (2018). https://doi.org/10.1007/s12094-018-1847-y

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  • DOI: https://doi.org/10.1007/s12094-018-1847-y

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