Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report

Abstract Background RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability,...

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Autores principales:	Mashu Futagawa, Hideki Yamamoto, Mariko Kochi, Yusaku Urakawa, Reimi Sogawa, Fumino Kato, Mika Okazawa-Sakai, Daisuke Ennishi, Katsunori Shinozaki, Hirofumi Inoue, Hiroyuki Yanai, Akira Hirasawa
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	RAD51D Splice variant Leiomyosarcoma Homologous recombination (HR) Cancer susceptibility Presumed germline pathogenic variant (PGPV) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/44be1e99494e4db990fec38e106ce428
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spelling	oai:doaj.org-article:44be1e99494e4db990fec38e106ce4282021-11-28T12:40:43ZRetroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report10.1186/s13053-021-00205-x1897-4287https://doaj.org/article/44be1e99494e4db990fec38e106ce4282021-11-01T00:00:00Zhttps://doi.org/10.1186/s13053-021-00205-xhttps://doaj.org/toc/1897-4287Abstract Background RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. Case presentation A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. Conclusions We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.Mashu FutagawaHideki YamamotoMariko KochiYusaku UrakawaReimi SogawaFumino KatoMika Okazawa-SakaiDaisuke EnnishiKatsunori ShinozakiHirofumi InoueHiroyuki YanaiAkira HirasawaBMCarticleRAD51DSplice variantLeiomyosarcomaHomologous recombination (HR)Cancer susceptibilityPresumed germline pathogenic variant (PGPV)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282GeneticsQH426-470ENHereditary Cancer in Clinical Practice, Vol 19, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RAD51D Splice variant Leiomyosarcoma Homologous recombination (HR) Cancer susceptibility Presumed germline pathogenic variant (PGPV) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Genetics QH426-470
spellingShingle	RAD51D Splice variant Leiomyosarcoma Homologous recombination (HR) Cancer susceptibility Presumed germline pathogenic variant (PGPV) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Genetics QH426-470 Mashu Futagawa Hideki Yamamoto Mariko Kochi Yusaku Urakawa Reimi Sogawa Fumino Kato Mika Okazawa-Sakai Daisuke Ennishi Katsunori Shinozaki Hirofumi Inoue Hiroyuki Yanai Akira Hirasawa Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
description	Abstract Background RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. Case presentation A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. Conclusions We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.
format	article
author	Mashu Futagawa Hideki Yamamoto Mariko Kochi Yusaku Urakawa Reimi Sogawa Fumino Kato Mika Okazawa-Sakai Daisuke Ennishi Katsunori Shinozaki Hirofumi Inoue Hiroyuki Yanai Akira Hirasawa
author_facet	Mashu Futagawa Hideki Yamamoto Mariko Kochi Yusaku Urakawa Reimi Sogawa Fumino Kato Mika Okazawa-Sakai Daisuke Ennishi Katsunori Shinozaki Hirofumi Inoue Hiroyuki Yanai Akira Hirasawa
author_sort	Mashu Futagawa
title	Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
title_short	Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
title_full	Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
title_fullStr	Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
title_full_unstemmed	Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
title_sort	retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant rad51d c.904-2a > t: a case report
publisher	BMC
publishDate	2021
url	https://doaj.org/article/44be1e99494e4db990fec38e106ce428
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Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report

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