Inherited susceptibility to uterine leiomyomas and renal cell cancer

Launonen, Virpi; Vierimaa, Outi; Kiuru, Maija; Isola, Jorma; Roth, Stina; Pukkala, Eero; Sistonen, Pertti; Herva, Riitta; Aaltonen, Lauri A.

doi:10.1073/pnas.051633798

Cited by 675Uterine Myomas and TreatmentsRenal cell carcinoma treatmentTuberous Sclerosis Complex Research

Inherited susceptibility to uterine leiomyomas and renal cell cancer

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Launonen, Virpi, Vierimaa, Outi, Kiuru, Maija, Isola, Jorma, Roth, Stina, Pukkala, Eero, Sistonen, Pertti, Herva, Riitta +1 more·2001·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.051633798PMC PMC30663

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Abstract

Herein we report the clinical, histopathological, and molecular features of a cancer syndrome with predisposition to uterine leiomyomas and papillary renal cell carcinoma. The studied kindred included 11 family members with uterine leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases occurred in young (33- to 48-year-old) females and displayed a unique natural history. All these kidney cancers displayed a distinct papillary histology and presented as unilateral solitary lesions that had metastasized at the time of diagnosis. Genetic-marker analysis mapped the predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histological features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papillary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer ( HLRCC ) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor suppressor. Clinical, histopathological, and molecular tools are now available for accurate detection and diagnosis of this cancer syndrome.

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Fumarate hydratase inactivation mutation was discovered in renal cell cancer and leads to fumarate accumulation in skin cancer, uterine leiomyomas, breast, bladder, and Leydig cell tumors.
“In 2001, mutation of fumarate hydratase leading to its inactivation was discovered in renal cell cancer129. Mutation of this enzyme leads to fumarate accumulation not only in skin cancer and uterine leiomyomas but also in breast, bladder, and Leydig cell tumors130.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [129]

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22. Hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report
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Authors: Launonen, V., Vierimaa, O., Kiuru, M., Isola, J., Roth, S., Pukkala, E., Sistonen, P., Herva, R., & Aaltonen, L. A.
Affiliations: University of Helsinki (FI)
Department of Medical Genetics, Haartman Institute, University of Helsinki, P. O. Box 21, FIN-00014, Helsinki, Finland; Department of Clinical Genetics, Oulu University Hospital, Kajaanintie 50, FIN-90220, Oulu, Finland; Institute of Medical Technology, University of Tampere, FIN-33014, Tampere, Finland; Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, FIN-00170, Helsinki, Finland; Finnish Red Cross Blood Transfusion Service,...
ORCID: Kiuru, Maija
Isola, Jorma
Pukkala, Eero
Aaltonen, Lauri A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-02-27
Volume: 98
Issue: 6
Pages: 3387-3392
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.051633798
PMC: PMC30663
OpenAlex: W2110394707
Cited by: 669
References: 24
Citations by year: 2026: 9 · 2025: 21 · 2024: 21 · 2023: 27 · 2022: 23 · 2021: 35 · 2020: 30 · 2019: 38 · 2018: 33 · 2017: 40 · 2016: 30 · 2015: 47 · 2014: 27 · 2013: 35 · 2012: 30
FWCI: 18.01
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Uterine Myomas and Treatments
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
Keywords: hereditary leiomyomatosis and renal cell carcinoma, uterine fibroids, papillary renal cell carcinoma, uterine leiomyosarcoma, tumor suppressor, hereditary cancer predisposition, dominant inheritance, metastatic renal cell carcinoma, histopathological diagnosis
MeSH terms: Adult, Carcinoma, Renal Cell, Chromosomes, Human, Female, Genetic Markers, Humans, Kidney Neoplasms, Leiomyoma, Leiomyosarcoma, Male, Middle Aged, Pedigree, Phenotype, Uterine Neoplasms, Genetic Predisposition to Disease

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Inherited susceptibility to uterine leiomyomas and renal cell cancer

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