Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors

Elizabeth Petri Henske, Lisa L. Wessner, Jeffrey Golden, Bernd W. Scheithauer, Alexander Vortmeyer, Zhengping Zhuang, Andres J.P. Klein-Szanto, David J. Kwiatkowski, Raymond S. Yeung

Research output: Contribution to journalArticle

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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and tumors of skin, brain, heart, and kidney. In this study, we focused on two of the most frequent tumors in TSC patients, renal angiomyolipomas and subependymal giant cell astrocytomas (SEGAs). Two questions were addressed. First, is loss of tuberin, the product of the TSC2 gene, seen in both renal and central nervous system tumors from TSC patients? Second, when loss of tuberin occurs, does it affect each of the cell types seen in these tumors? We used a loss of heterozygosity approach to identify tumors from TSC2 patients. We found loss of tuberin immunostaining in the spindle and epithelioid cells but not in the giant cells of six TSC2 SEGAs. We also found loss of tuberin immunostaining in all three cell types (smooth muscle, fat, and vessels) of six TSC2 angiomyolipomas. Chromosome 16p13 loss of heterozygosity occurred in both spindle and epithelioid cells of a SEGA and in smooth muscle and fat but not the vessels of two angiomyolipomas. These results support a two-hit tumor suppressor model for the pathogenesis of SEGAs and angiomyolipomas. The vascular elements of angiomyolipomas and the giant cells of SEGAs may be reactive rather than neoplastic.

Original languageEnglish (US)
Pages (from-to)1639-1647
Number of pages9
JournalAmerican Journal of Pathology
Volume151
Issue number6
StatePublished - Dec 1 1997
Externally publishedYes

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Angiomyolipoma
Tuberous Sclerosis
Astrocytoma
Epithelioid Cells
Loss of Heterozygosity
Giant Cells
Neoplasms
Kidney
Fats
Central Nervous System Neoplasms
Brain Neoplasms
Intellectual Disability
Smooth Muscle Myocytes
Smooth Muscle
Blood Vessels
Epilepsy
Chromosomes
tuberous sclerosis complex 2 protein
Skin
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. / Henske, Elizabeth Petri; Wessner, Lisa L.; Golden, Jeffrey; Scheithauer, Bernd W.; Vortmeyer, Alexander; Zhuang, Zhengping; Klein-Szanto, Andres J.P.; Kwiatkowski, David J.; Yeung, Raymond S.

In: American Journal of Pathology, Vol. 151, No. 6, 01.12.1997, p. 1639-1647.

Research output: Contribution to journalArticle

Henske, EP, Wessner, LL, Golden, J, Scheithauer, BW, Vortmeyer, A, Zhuang, Z, Klein-Szanto, AJP, Kwiatkowski, DJ & Yeung, RS 1997, 'Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors', American Journal of Pathology, vol. 151, no. 6, pp. 1639-1647.
Henske, Elizabeth Petri ; Wessner, Lisa L. ; Golden, Jeffrey ; Scheithauer, Bernd W. ; Vortmeyer, Alexander ; Zhuang, Zhengping ; Klein-Szanto, Andres J.P. ; Kwiatkowski, David J. ; Yeung, Raymond S. / Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. In: American Journal of Pathology. 1997 ; Vol. 151, No. 6. pp. 1639-1647.
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