Neuroblastoma, pheochromocytoma, and renal cell carcinoma. Occurrence in a single patient

Fairchild, R. S.

doi:10.1001/jama.242.20.2210

Cited by 12 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore suggest that some neuroblastomas, like pheochromocytomas, result from germline alterations that directly or indirectly compromise KIF1B␤ function and allow certain neuronal progenitor cells to escape developmental culling. This model is consistent with the prediction, based on epidemiological studies, that at least ∼20% of pheochromocytomas and neuroblastomas involve a hereditary component (Knudson and Strong 1972;Knudson and Meadows 1976) and could account for previously described patients (Fairchild et al 1979;Tatekawa et al 2006) who, like our patient with the S1481N variant, developed both of these otherwise rare tumors as children or young adults. KIF1B␣ and KIF1B␤ are motor proteins implicated in anterograde transport of mitochondria and synaptic vesicle precursors, respectively (Nangaku et al 1994;Zhao et al 2001).…”

Section: Discussionsupporting

confidence: 93%

The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor

Schlisio¹,

Kenchappa²,

Vredeveld³

et al. 2008

Genes Dev.

307

292

View full text Add to dashboard Cite

VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural crest-derived tumors. Using an unbiased shRNA screen we found that the kinesin KIF1B␤ acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. KIF1B␤ maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function KIF1B␤ missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that KIF1B␤ is a pathogenic target of these deletions.[Keywords: Apoptosis; kinesin; neuroblastoma; pheochromocytoma; prolyl hydroxylase] Supplemental material is available at http://www.genesdev.org.

show abstract

Section: Discussionsupporting

confidence: 93%

The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor

Schlisio¹,

Kenchappa²,

Vredeveld³

et al. 2008

Genes Dev.

307

292

View full text Add to dashboard Cite

show abstract

“…Another 12 cases of renal cell carcinoma associated with neuroblastoma have now been reported in the literature. 12,[15][16][17]26,27 The cytogenetic and microsatellite PCR analyses performed on the four oncocytoid renal cell carcinomas reported by Medeiros et al 30 revealed abnormalities not usually described in other known types of renal cell carcinoma. In accordance, absence of TFE3 overexpression, MSI, and VHL alterations in our study support the concept of these carcinomas as a distinct clinicopathologic entity now included in the new WHO classification.…”

Section: Discussionmentioning

confidence: 93%

Morphologic and Molecular Characterization of Renal Cell Carcinoma in Children and Young Adults

Bruder¹,

Passera²,

Harms³

et al. 2004

American Journal of Surgical Pathology

243

193

View full text Add to dashboard Cite

A new WHO classification of renal cell carcinoma has been introduced in 2004. This classification includes the recently described renal cell carcinomas with the ASPL-TFE3 gene fusion and carcinomas with a PRCC-TFE3 gene fusion. Collectively, these tumors have been termed Xp11.2 or TFE3 translocation carcinomas, which primarily occur in children and young adults. To further study the characteristics of renal cell carcinoma in young patients and to determine their genetic background, 41 renal cell carcinomas of patients younger than 22 years were morphologically and genetically characterized. Loss of heterozygosity analysis of the von Hippel-Lindau gene region and screening for VHL gene mutations by direct sequencing were performed in 20 tumors. TFE3 protein overexpression, which correlates with the presence of a TFE3 gene fusion, was assessed by immunohistochemistry. Applying the new WHO classification for renal cell carcinoma, there were 6 clear cell (15%), 9 papillary (22%), 2 chromophobe, and 2 collecting duct carcinomas. Eight carcinomas showed translocation carcinoma morphology (20%). One carcinoma occurred 4 years after a neuroblastoma. Thirteen tumors could not be assigned to types specified by the new WHO classification: 10 were grouped as unclassified (24%), including a unique renal cell carcinoma with prominently vacuolated cytoplasm and WT1 expression. Three carcinomas occurred in combination with nephroblastoma. Molecular analysis revealed deletions at 3p25-26 in one translocation carcinoma, one chromophobe renal cell carcinoma, and one papillary renal cell carcinoma. There were no VHL mutations. Nuclear TFE3 overexpression was detected in 6 renal cell carcinomas, all of which showed areas with voluminous cytoplasm and foci of papillary architecture, consistent with a translocation carcinoma phenotype. The large proportion of TFE3 "translocation" carcinomas and "unclassified" carcinomas in the first two decades of life demonstrates that renal cell carcinomas in young patients contain genetically and phenotypically distinct tumors with further potential for novel renal cell carcinoma subtypes. The far lower frequency of clear cell carcinomas and VHL alterations compared with adults suggests that renal cell carcinomas in young patients have a unique genetic background.

show abstract

“…22 The combination of NB, PGL and renal cell carcinoma was first described by Fairchild et al 23 Most recently, the case of a patient who was found to have at the same time malignant NB, PHEO and renal cell carcinoma was described; sequence analysis revealed an SDHB mutation. 24 In another patient with NB and a PGL, a germline SDHB gene deletion was found.…”

Section: Discussionmentioning

confidence: 99%

Carney triad can be (rarely) associated with germline succinate dehydrogenase defects

et al. 2015

View full text Add to dashboard Cite

Carney triad, the association of paragangliomas/pheochromocytomas, gastrointestinal stromal tumors and pulmonary chondromas, is a sporadic condition that is significantly more frequent in females; its genetic etiology remains unknown. Carney triad is distinct from the dyad of paragangliomas/pheochromocytomas and gastrointestinal stromal tumors, known as Carney-Stratakis syndrome, which is inherited in an autosomal-dominant manner and is almost always caused by succinate dehydrogenase subunit mutations. In the present study, we investigated the largest cohort of Carney triad patients that is available internationally: 63 unrelated patients. Six patients (9.5%) were found to have germline variants in the SDHA, SDHB or SDHC genes. All six patients, except one, had multifocal gastrointestinal stromal tumors, chondromas and/or paragangliomas. A patient with Carney triad and SDHC variant had a ganglioneuroma. One of the patients with Carney triad and SDHB mutation had a nephew with the same sequence defect, who developed a neuroblastoma. Other relatives, carriers of the identified SDHA, SDHB or SDHC mutations, have not developed any of the components of Carney triad or Carney-Stratakis syndrome. None of the other 57 Carney triad patients had any genomic defects of SDHA, SDHB or SDHC genes. We conclude that, in rare occasions, Carney triad can be allelic to Carney-Stratakis syndrome. Although for the vast majority of patients with Carney triad the causative defect(s) remain(s) unknown, testing for SDHA, SDHB or SDHC variations should be offered, as carriers may develop isolated paragangliomas/pheochromocytomas and occasionally other tumors.

show abstract

Neuroblastoma, pheochromocytoma, and renal cell carcinoma. Occurrence in a single patient

Cited by 12 publications

References 0 publications

The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor

The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor

Morphologic and Molecular Characterization of Renal Cell Carcinoma in Children and Young Adults

Carney triad can be (rarely) associated with germline succinate dehydrogenase defects

Contact Info

Product

Resources

About