Familial and Sporadic Renal Oncocytomas &amp;ndash; A Comparative Molecular&amp;ndash;Genetic Analysis

Junker, Kerstin; Weirich, Gregor; Morávek, P; Podhola, M; Ilse, B.; Hartmann, Arndt; Schubert, Jöerg

doi:10.1159/000049795

Cited by 24 publications

(12 citation statements)

References 26 publications

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“…In addition, evidence of a recently described abnormality of chromosome 19 (chromosomal gains and somatically paired chromosomes) was also apparent in both chromophobe RCC and renal oncocytoma data [47]. Though we predicted one BHDS-derived tumor sample (BHD4, Additional file 1, Table S1) contains multiple abnormalities involving chromosomes 2, 3, 4, 5, 6, 13, and 18, a phenomenon that is sometimes observed in sporadic cases of renal oncocytoma [48], the tumor possessed histology typical of hybrid oncocytic-chromophobe BHDS-derived tumors (Additional file 2, Figures S3A-B). The BHDS-derived tumors appeared mostly devoid of chromosomal abnormalities that are typical of the sporadic tumors.…”

Section: Resultsmentioning

confidence: 74%

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

et al. 2010

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BackgroundGermline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied.MethodsBHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets.ResultsRenal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression.ConclusionsOur results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1α-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function.

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Section: Resultsmentioning

confidence: 74%

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

et al. 2010

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“…A molecular-genetic analysis from Junker et al suggested that 87% of familial oncocytoma were devoid of chromosomal instabilities. 17 …”

Section: Discussionmentioning

confidence: 99%

The Impact of Germline BHD Mutation on Histological Concordance and Clinical Treatment of Patients With Bilateral Renal Masses and Known Unilateral Oncocytoma

et al. 2011

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Introduction and Objective Managing patients presenting with oncocytoma in the setting of bilateral renal masses is a challenging scenario. Nevertheless, pathologic concordance of oncocytic neoplasm in one kidney with tumors in the contralateral kidney is not known. We aim to evaluate the influence of germline Birt-Hogg-Dubé (BHD) mutation on concordance rates to assist in management of these patients. Methods We reviewed records of the NIH patients between 1983 and 2009 having bilateral renal masses, known pathology bilaterally, and presence of oncocytoma or oncocytic neoplasm in at least one kidney. The presence of oncocytoma or oncocytic neoplasm in two renal units was considered concordant. Demographic, pathological and clinical data were collected. Results The patient population consisted of 40 patients: 23 with BHD and 17 patients without diagnosis of BHD. Patients with BHD were younger (p<0.01) but there were no other differences between two groups. However, patients with BHD had a statistically lower histologic concordance between bilateral masses when compared to patients without the diagnosis of BHD (Fisher's exact test, p<0.01). Additionally, the subgroup of patients (n=8) without BHD who had multifocal renal masses demonstrated 100% oncocytoma concordance between renal units. Conclusions In patients with bilateral renal masses BHD patients have significantly lower histologic concordance rates compared to patients without BHD. Patients with BHD should be monitored and managed differently than patients without detected genetic mutations, especially those with multifocal oncocytomas. Genetic testing for BHD should be considered in the algorithm for management of patients with bilateral renal masses and known oncocytoma.

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“…The genetic associations are: (i) loss of chromosome Y or monosomy 1, (ii) translocations in the 11q13 area and (iii) genetic abnormalities such as trisomy, monosomy and/or a loss of heterozygosity. 5 These genetic changes are specific for oncocytoma and are not seen in RCC. 6 On gross appearance, these tumours are cortically localized, light brown or tan, homogenous, well circumscribed with a commonly seen central scar.…”

Section: Discussionmentioning

confidence: 99%

Case report of a symptomatic giant renal oncocytoma

Ahmad

Manecksha

Hayes

et al. 2011

International Journal of Surgery Case Reports

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Renal oncocytomas are benign tumours, often asymptomatic, and picked incidentally on radiological imaging. We present a case report of a symptomatic giant renal oncocytoma in a 61-year old man having lower back/right flank pain. A large right renal mass was identified on abdominal CT scan. Radiological features were not sufficient to differentiate this lesion from renal cancer. Right radical nephrectomy was performed. Typical features of oncocytoma, without evidence of malignancy, were seen on histological examination of the specimen. In this report, we discuss literature review of radiological, genetic, and pathological characteristics of renal oncocytoma.

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Familial and Sporadic Renal Oncocytomas – A Comparative Molecular–Genetic Analysis

Cited by 24 publications

References 26 publications

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

The Impact of Germline BHD Mutation on Histological Concordance and Clinical Treatment of Patients With Bilateral Renal Masses and Known Unilateral Oncocytoma

Case report of a symptomatic giant renal oncocytoma

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