Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas

Barker, K T; Bevan, Steve; Wang, R; Lu, Ye; Flanagan, Adrienne M.; Bridge, J A; Fisher, Cyril; Finlayson, C.; Shipley, Janet; Houlston, Richard S.

doi:10.1038/sj.bjc.6600502

Cited by 54 publications

(41 citation statements)

References 12 publications

(2 reference statements)

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“…Seventeen percent of tumors showed AI at 1q43. Barker et al (2002) reported AI at 1q in half of the analyzed ULMS, but in some of the cases AI was not confined to the vicinity of FH. 23 In addition, in previous CGH analyses of ULMSs, chromosomal gains at 1q have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Barker et al (2002) reported AI at 1q in half of the analyzed ULMS, but in some of the cases AI was not confined to the vicinity of FH. 23 In addition, in previous CGH analyses of ULMSs, chromosomal gains at 1q have been reported. [3][4][5] Thus, it is possible that another yet unidentified gene at 1q is involved in tumorigenesis of ULMS.…”

Section: Discussionmentioning

confidence: 99%

“…20,24 Barker et al (2002Barker et al ( , 2005 analyzed altogether 35 ULMSs but no FH mutations were found. 23,26 Here too, no somatic mutations were identified in ULMSs. However, based on this and previous works by us FH is clearly involved in genesis of a subset of early onset ULMSs, especially in the context of the HLRCC syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…20,[23][24][25][26] Thus far, only 3 somatic FH mutations have been identified, in 1 soft-tissue sarcoma and 2 uterine leiomyomas. 20,24 Barker et al (2002Barker et al ( , 2005 analyzed altogether 35 ULMSs but no FH mutations were found. 23,26 Here too, no somatic mutations were identified in ULMSs.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of fumarate hydratase mutations in a population‐based series of early onset uterine leiomyosarcoma patients

Ylisaukko-oja

Kiuru

Lehtonen

et al. 2006

Intl Journal of Cancer

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Germline mutations in fumarate hydratase (FH) gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. In HLRCC, the most common clinical features are leiomyomas of the skin and uterus, and in a subset of the families, renal cell cancer (RCC) and uterine leiomyosarcoma (ULMS) occur frequently at young age. This study was conducted to evaluate the possible contribution of FH mutations in a population-based series of early onset (45 years) ULMSs. Eighty-one cases were identified through the national cancer registry, and samples from 67 cases (83%) were available for FH mutation screening and analysis of allelic imbalance (AI) at the FH locus. Seventeen percent of tumors showed AI. In the mutation analysis, a novel missense mutation K424R was found. The mutation was also found from the patient's normal tissue. To study whether this variant has functional consequences, FH enzyme activity assay was performed in a cell model. The activity of the mutated protein was significantly reduced as compared to wild type (p 5 0.009). This study shows that FH germline mutations can occur in seemingly nonsyndromic cases of ULMS (1/67, 1.5%). It appears that on the population level hereditary FH defects do play a role in pathogenesis of sporadic early onset ULMSs, albeit rarely. ' 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Analysis of fumarate hydratase mutations in a population‐based series of early onset uterine leiomyosarcoma patients

Ylisaukko-oja

Kiuru

Lehtonen

et al. 2006

Intl Journal of Cancer

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“…Die häufiger vorkommenden, in der Regel größeren (>5 cm), selten schmerzhaften, tief dermalen bis subkutan gelegenen LMS weisen eine 50%ige Lokalrezidivrate und eine hä-matogene Metastasierungshäufigkeit von 30-60% auf [2]; 25% metastasieren lymphogen [4]. Häufigster Metastasierungsort sind die Lungen, gefolgt von Leber und Skelett [5].…”

Section: Diskussionunclassified

Unterschiedliche Charakteristika subkutaner und dermaler Leiomyosarkome

Seemann

Lehmann

2006

Hautarzt

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Cutaneous leiomyosarcomas (LMS) originating from smooth muscle of the skin are rare malignant neoplasms. Preferential sites are hair-bearing areas, especially the legs. We report two patients in their 5th and 7th decade, in whom leiomyosarcomas were encountered in the lower leg and the capillitium, respectively. Histologically, the former was found to be a dermal leiomyosarcoma with subcutaneous infiltration, the latter an exclusively dermal tumor. The LMS of the lower leg had been excised three years previously in a different institution and had been diagnosed as a leiomyoma. Both lesions were excised with adequate safety margins in our institution and within a two-year postoperative observation period no recurrences were encountered. Dermal leiomyosarcomas have a 33% recurrence rate while that of subcutaneous leiomyosarcomas show is 50%. In contrast to exclusively dermal tumors, subcutaneous LMS show a tendency for hematogenic and lymphogenic metastases. Therapy of choice is excision with wide safety margins.

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Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: Genetic linkage analysis and FISH studies

Gross

Panhuysen

Kleinman

et al. 2004

Genes Chromosomes & Cancer

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Recently, germline mutations of the fumarate hydratase (FH) gene, in 1q42.1, have been found to be involved in syndromes associated with uterine leiomyomas (ULs). Compelling evidence also supports a genetic liability to develop nonsyndromic UL, although susceptibility genes have not been reported to date. Loss of heterozygosity (LOH) studies have found no or rare evidence of LOH of FH in nonsyndromic UL. However, the karyotypes of these tumors were not reported, and cytogenetic aberrations of 1q42-44 have been observed infrequently in UL. To determine whether FH mutations also may predispose women to developing nonsyndromic UL, we performed a genetic linkage study with DNA from 123 families containing at least one affected sister pair. In addition, to assess the frequency of FH loss specifically in UL with 1q rearrangements, we performed a fluorescence in situ hybridization (FISH) analysis of UL with 1q rearrangements. Analysis of the genotyping data revealed evidence suggestive of linkage to the FH region among study participants who were less than 40 years of age at diagnosis (Zlr 1.7 at D1S547, P = 0.04). FISH results showed that one copy of FH was absent in 9 of 11 ULs. These data indicate that loss of FH might be a significant event in the pathogenesis of a subset of nonsyndromic ULs.

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Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas

Cited by 54 publications

References 12 publications

Analysis of fumarate hydratase mutations in a population‐based series of early onset uterine leiomyosarcoma patients

Analysis of fumarate hydratase mutations in a population‐based series of early onset uterine leiomyosarcoma patients

Unterschiedliche Charakteristika subkutaner und dermaler Leiomyosarkome

Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: Genetic linkage analysis and FISH studies

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