Case of hereditary leiomyomatosis and renal cell cancer showing multiple cutaneous leiomyomas harboring a recurrent nonsense mutation in the fumarate hydratase gene

2021 ◽  
Author(s):  
Shoko Mai ◽  
Teruki Yanagi ◽  
Mayuna Shimano ◽  
Wataru Nishie ◽  
Ken Arita ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Nonsense Mutation ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Cutaneous Leiomyomas ◽  
Hereditary Leiomyomatosis

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.

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.

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