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Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene.
BMC Med Genet. 2018 01 31; 19(1):20.BM

Abstract

BACKGROUND

Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML.

CASE PRESENTATION

We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay.

CONCLUSIONS

We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases.

Authors+Show Affiliations

Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. deniss@elitekliinik.ee. Elite Clinic, Sangla 63, 50407, Tartu, Estonia. deniss@elitekliinik.ee. Competence Centre on Health Technologies, Tartu, Estonia. deniss@elitekliinik.ee.Competence Centre on Health Technologies, Tartu, Estonia. Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.Department of Pathology, Tartu University Hospital, Tartu, Estonia.Department of Pathology, Tartu University Hospital, Tartu, Estonia.Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. Competence Centre on Health Technologies, Tartu, Estonia.Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. Elite Clinic, Sangla 63, 50407, Tartu, Estonia. Tartu University Hospital's Women's Clinic, Tartu, Estonia.Department of Pulmonary Medicine, University of Tartu, Tartu, Estonia. Lung Clinic, Tartu University Hospital, Tartu, Estonia.Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. Competence Centre on Health Technologies, Tartu, Estonia. Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia. Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. Competence Centre on Health Technologies, Tartu, Estonia.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29386003

Citation

Sõritsa, Deniss, et al. "Whole Exome Sequencing of Benign Pulmonary Metastasizing Leiomyoma Reveals Mutation in the BMP8B Gene." BMC Medical Genetics, vol. 19, no. 1, 2018, p. 20.
Sõritsa D, Teder H, Roosipuu R, et al. Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene. BMC Med Genet. 2018;19(1):20.
Sõritsa, D., Teder, H., Roosipuu, R., Tamm, H., Laisk-Podar, T., Soplepmann, P., Altraja, A., Salumets, A., & Peters, M. (2018). Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene. BMC Medical Genetics, 19(1), 20. https://doi.org/10.1186/s12881-018-0537-5
Sõritsa D, et al. Whole Exome Sequencing of Benign Pulmonary Metastasizing Leiomyoma Reveals Mutation in the BMP8B Gene. BMC Med Genet. 2018 01 31;19(1):20. PubMed PMID: 29386003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene. AU - Sõritsa,Deniss, AU - Teder,Hindrek, AU - Roosipuu,Retlav, AU - Tamm,Hannes, AU - Laisk-Podar,Triin, AU - Soplepmann,Pille, AU - Altraja,Alan, AU - Salumets,Andres, AU - Peters,Maire, Y1 - 2018/01/31/ PY - 2017/06/28/received PY - 2018/01/24/accepted PY - 2018/2/2/entrez PY - 2018/2/2/pubmed PY - 2018/12/18/medline KW - BMP8B KW - Benign metastasizing leiomyoma KW - Endometriosis KW - GnRH agonists KW - Pulmonary lesion KW - Somatic gene mutation SP - 20 EP - 20 JF - BMC medical genetics JO - BMC Med. Genet. VL - 19 IS - 1 N2 - BACKGROUND: Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML. CASE PRESENTATION: We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay. CONCLUSIONS: We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/29386003/Whole_exome_sequencing_of_benign_pulmonary_metastasizing_leiomyoma_reveals_mutation_in_the_BMP8B_gene_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0537-5 DB - PRIME DP - Unbound Medicine ER -