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Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RC...

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Autores principales: Ueki, Arisa, Sugano, Kokichi, Misu, Kumiko, Aimono, Eriko, Nakamura, Kohei, Tanishima, Shigeki, Tanaka, Nobuyuki, Mikami, Shuji, Hirasawa, Akira, Ando, Miho, Yoshida, Teruhiko, Oya, Mototsugu, Nishihara, Hiroshi, Kosaki, Kenjiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347438/
https://www.ncbi.nlm.nih.gov/pubmed/34360727
http://dx.doi.org/10.3390/ijms22157962
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author Ueki, Arisa
Sugano, Kokichi
Misu, Kumiko
Aimono, Eriko
Nakamura, Kohei
Tanishima, Shigeki
Tanaka, Nobuyuki
Mikami, Shuji
Hirasawa, Akira
Ando, Miho
Yoshida, Teruhiko
Oya, Mototsugu
Nishihara, Hiroshi
Kosaki, Kenjiro
author_facet Ueki, Arisa
Sugano, Kokichi
Misu, Kumiko
Aimono, Eriko
Nakamura, Kohei
Tanishima, Shigeki
Tanaka, Nobuyuki
Mikami, Shuji
Hirasawa, Akira
Ando, Miho
Yoshida, Teruhiko
Oya, Mototsugu
Nishihara, Hiroshi
Kosaki, Kenjiro
author_sort Ueki, Arisa
collection PubMed
description Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient’s family was advised to undergo genetic counseling to consider additional RCC screening.
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spelling pubmed-83474382021-08-08 Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling Ueki, Arisa Sugano, Kokichi Misu, Kumiko Aimono, Eriko Nakamura, Kohei Tanishima, Shigeki Tanaka, Nobuyuki Mikami, Shuji Hirasawa, Akira Ando, Miho Yoshida, Teruhiko Oya, Mototsugu Nishihara, Hiroshi Kosaki, Kenjiro Int J Mol Sci Case Report Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient’s family was advised to undergo genetic counseling to consider additional RCC screening. MDPI 2021-07-26 /pmc/articles/PMC8347438/ /pubmed/34360727 http://dx.doi.org/10.3390/ijms22157962 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Ueki, Arisa
Sugano, Kokichi
Misu, Kumiko
Aimono, Eriko
Nakamura, Kohei
Tanishima, Shigeki
Tanaka, Nobuyuki
Mikami, Shuji
Hirasawa, Akira
Ando, Miho
Yoshida, Teruhiko
Oya, Mototsugu
Nishihara, Hiroshi
Kosaki, Kenjiro
Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title_full Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title_fullStr Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title_full_unstemmed Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title_short Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling
title_sort germline whole-gene deletion of fh diagnosed from tumor profiling
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347438/
https://www.ncbi.nlm.nih.gov/pubmed/34360727
http://dx.doi.org/10.3390/ijms22157962
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