Prospective Detection of Germline Mutation of Fumarate Hydratase in Women With Uterine Smooth Muscle Tumors Using Pathology-based Screening to Trigger Genetic Counseling for Hereditary Leiomyomatosis Renal Cell Carcinoma Syndrome

2019 ◽  
Vol 43 (5) ◽  
pp. 639-655 ◽  
Author(s):  
Joseph T. Rabban ◽  
Emily Chan ◽  
Julie Mak ◽  
Charles Zaloudek ◽  
Karuna Garg
Keyword(s):  
Renal Cell Carcinoma ◽  
Smooth Muscle ◽  
Genetic Counseling ◽  
Cell Carcinoma ◽  
Germline Mutation ◽  
Renal Cell ◽  
Fumarate Hydratase ◽  
Uterine Smooth Muscle ◽  
Smooth Muscle Tumors ◽  
Hereditary Leiomyomatosis

scholarly journals A novel pathogenic variant of the FH gene in a family with hereditary leiomyomatosis and renal cell carcinoma

2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Yasuto Yagi ◽  
Naoko Abeto ◽  
Junichi Shiraishi ◽  
Chieko Miyata ◽  
Satomi Inoue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Pathogenic Variant ◽  
Loss Of Function ◽  
Healthy Siblings ◽  
Surveillance Programs ◽  
Hereditary Leiomyomatosis

AbstractHereditary leiomyomatosis and renal cell carcinoma caused by loss-of-function germline variants of the FH gene can develop into aggressive renal cell carcinoma (RCC). We report the case of a 27-year-old man who died of RCC. Genetic testing revealed a novel pathogenic variant of FH, NM_000143.3:c.1013_1014del (p.Ile338Serfs*3), that was also identified in healthy siblings. Identification of genetic causes in the proband helped us to provide relatives with precise genetic counseling and appropriate surveillance programs.

scholarly journals Metabolic Reprogramming for Producing Energy and Reducing Power in Fumarate Hydratase Null Cells from Hereditary Leiomyomatosis Renal Cell Carcinoma

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72179 ◽  
Author(s):  
Youfeng Yang ◽  
Andrew N. Lane ◽  
Christopher J. Ricketts ◽  
Carole Sourbier ◽  
Ming-Hui Wei ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fumarate Hydratase ◽  
Reducing Power ◽  
Metabolic Reprogramming ◽  
Hereditary Leiomyomatosis

scholarly journals Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC): A Contemporary Review and Practical Discussion of the Differential Diagnosis for HLRCC-Associated Renal Cell Carcinoma

2018 ◽  
Vol 142 (10) ◽  
pp. 1202-1215 ◽  
Author(s):  
Stephanie L. Skala ◽  
Saravana M. Dhanasekaran ◽  
Rohit Mehra
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fumarate Hydratase ◽  
Molecular Testing ◽  
University Of Michigan ◽  
Architectural Patterns ◽  
Aggressive Clinical Course ◽  
Inactivating Mutations ◽  
Hereditary Leiomyomatosis

Context.— Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is an uncommon disorder with germline-inactivating mutations in the fumarate hydratase (FH) gene. The kidney cancers that develop in patients with HLRCC are often unilateral and solitary, with a potentially aggressive clinical course; morphologic identification of suspicious cases is of the utmost importance. Objective.— To review classic morphologic features of HLRCC-associated renal cell carcinoma, the reported morphologic spectrum of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in diagnosis of these tumors. Data Sources.— University of Michigan cases and review of pertinent literature about HLRCC and the morphologic spectrum of HLRCC-associated renal cell carcinoma. Conclusions.— Histologic features, such as prominent nucleoli with perinucleolar halos and multiple architectural patterns within one tumor, are suggestive of HLRCC-associated renal cell carcinoma. However, the morphologic spectrum is broad. Appropriate use of FH immunohistochemistry and referral to genetic counseling is important for detection of this syndrome.

scholarly journals A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy

2020 ◽  
Vol 7 (2) ◽  
pp. 6-10
Author(s):  
Ichiro Yonese ◽  
Masaya Ito ◽  
Kosuke Takemura ◽  
Takao Kamai ◽  
Fumitaka Koga
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Cancer Syndrome ◽  
Durable Response ◽  
Pelvic Cancer ◽  
Hereditary Leiomyomatosis

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal prognosis. We report a case of metastatic HLRCC-associated RCC in a 65-year-old Japanese male whose clinical features mimicked advanced renal pelvic cancer. A durable response was achieved with a sequence of axitinib and nivolumab after cytoreductive and diagnostic nephrectomy. Their potential therapeutic roles in the management of metastatic HLRCC-associated RCC have been discussed based on its molecular and biological backgrounds.

scholarly journals Hereditary Leiomyomatosis and Renal Cell Cancer: Recent Insights Into Mechanisms and Systemic Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Congwang Zhang ◽  
Lijun Li ◽  
Yipeng Zhang ◽  
Changchun Zeng
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Underlying Mechanisms ◽  
Hereditary Leiomyomatosis

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare autosomal dominant hereditary cancer syndrome characterized by a predisposition to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). It is known to be caused by germline mutations of the fumarate hydratase (FH) gene, which encodes an enzyme component of the citric acid cycle and catalyzes the conversion of fumarate to L-malate. Currently, there is no standardized treatment for HLRCC, which may be due in part to a lack of understanding of the underlying mechanisms. Here, the underlying molecular mechanisms by which the inactivation of FH causes HLRCC are discussed. Additionally, potential therapeutic pharmacological strategies are also summarized to provide new perspectives for the prevention and treatment of HLRCC.

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