scholarly journals Association of Germline Mutations in the Fumarate Hydratase Gene and Uterine Fibroids in Women With Hereditary Leiomyomatosis and Renal Cell Cancer

2008 ◽  
Vol 144 (12) ◽  
Author(s):  
Laveta Stewart ◽  
Gladys M. Glenn ◽  
Pamela Stratton ◽  
Alisa M. Goldstein ◽  
Maria J. Merino ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Uterine Fibroids ◽  
Germline Mutations ◽  
Hereditary Leiomyomatosis

Clinicopathological and molecular features of hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas

2020 ◽  
Vol 73 (12) ◽  
pp. 819-825 ◽  
Author(s):  
Mitsuko Furuya ◽  
Yasuhiro Iribe ◽  
Yoji Nagashima ◽  
Naotomo Kambe ◽  
Chisato Ohe ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Copy Number ◽  
Cell Cancer ◽  
Uniparental Disomy ◽  
Fumarate Hydratase ◽  
Germline Mutations ◽  
Molecular Features ◽  
Increased Risk ◽  
Hereditary Leiomyomatosis

AimsHereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by germline mutations in fumarate hydratase (FH). Affected families have an increased risk of renal cell carcinoma (RCC). HLRCC-associated RCC (HLRCC-RCC) is highly aggressive. Clinicopathological information of genetically diagnosed patients with HLRCC-RCC contributes to the establishment of effective therapies.MethodsTen Japanese patients with HLRCC-RCC were enrolled in the study. Genetic testing for FH was carried out. Somatic mutations in FH and immunohistochemical analyses of FH and B7 family ligands (PD-L1 and B7-H3) were investigated in 13 tumours. Copy number variations were evaluated in two tumours.ResultsAll patients had FH germline mutations. Regarding histology, most tumours had type 2 papillary architecture or tubulocystic pattern or both. All tumours were FH deficient by immunohistochemistry. Ten tumours were positive for PD-L1, and 12 tumours were positive for B7-H3. Somatic mutation analysis demonstrated loss of heterozygosity of FH in 10 tumours. Copy number variation analysis revealed uniparental disomy between 1q24.2 and 1q44 encompassing FH; gain of chromosome 2 p was also common. All patients had either metastases or residual tumours. Three patients died of HLRCC-RCC and one of colon cancer, whereas the other six are currently alive, including two without recurrence.ConclusionsHLRCC-RCCs appear to have unique molecular profiles, including PD-L1 expression. One patient had complete response to immunotherapy, which may be an option for HLRCC-RCC.

First Presentation of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Pregnancy

2016 ◽  
Vol 20 (4) ◽  
pp. 334-336
Author(s):  
Kathryn Woolner ◽  
Ashley O’Toole ◽  
Lauren LaBerge
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Case Series ◽  
Review Of The Literature ◽  
Cancer Syndrome ◽  
Cutaneous Lesions ◽  
Hereditary Leiomyomatosis ◽  
In Pregnancy

Background: Reed’s syndrome, also known as hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome, is an autosomal dominant condition in which affected individuals may develop cutaneous leiomyomas, uterine fibroids, and renal cell carcinoma. Objective: This report describes a unique case of HLRCC because it presented in pregnancy with development of cutaneous pilar leiomyomas. Methods: Review of the literature for previous cases of Reed’s syndrome during pregnancy including PubMed and Medline search. Results: Genetic testing of this patient demonstrated a mutation in the fumarate hydratase ( FH) gene. Review of the literature showed only 1 previous case series that described the onset of cutaneous lesions during pregnancy. Conclusion: This case serves as a reminder that there may exist a correlation between pregnancy and the first manifestation of cutaneous lesions in patients with HLRCC, and thus an increased clinical suspicion is warranted during this period.

scholarly journals Mutations in the Fumarate Hydratase Gene Cause Hereditary Leiomyomatosis and Renal Cell Cancer in Families in North America

2003 ◽  
Vol 73 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Jorge R. Toro ◽  
Michael L. Nickerson ◽  
Ming-Hui Wei ◽  
Michelle B. Warren ◽  
Gladys M. Glenn ◽  
...  
Keyword(s):  
North America ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Hereditary Leiomyomatosis

scholarly journals Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Benjamin T. Ristau ◽  
Sonal N. Kamat ◽  
Tatum V. Tarin
Keyword(s):  
Growth Factor ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Cystic Tumor ◽  
Precursor Lesion ◽  
Glucose Transporter 1 ◽  
Hereditary Leiomyomatosis

The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb’s cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of “pseudohypoxia,” inducing hypoxia inducible factor 1α(HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome.

scholarly journals Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas W. Bateman ◽  
Christopher M. Tarney ◽  
Tamara Abulez ◽  
Anthony R. Soltis ◽  
Ming Zhou ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Target Genes ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Thioredoxin Reductase ◽  
Antioxidant Response ◽  
Suppressor Gene ◽  
Uterine Leiomyomas ◽  
Hereditary Leiomyomatosis

AbstractPathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.

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