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Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma.
J Pathol. 2008 Feb; 214(3):387-93.JP

Abstract

Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma.

Authors+Show Affiliations

Department of Pathology, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan. ccpan@vghtpe.gov.twNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18085521

Citation

Pan, C-C, et al. "Constant Allelic Alteration On Chromosome 16p (TSC2 Gene) in Perivascular Epithelioid Cell Tumour (PEComa): Genetic Evidence for the Relationship of PEComa With Angiomyolipoma." The Journal of Pathology, vol. 214, no. 3, 2008, pp. 387-93.
Pan CC, Chung MY, Ng KF, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol. 2008;214(3):387-93.
Pan, C. C., Chung, M. Y., Ng, K. F., Liu, C. Y., Wang, J. S., Chai, C. Y., Huang, S. H., Chen, P. C., & Ho, D. M. (2008). Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. The Journal of Pathology, 214(3), 387-93.
Pan CC, et al. Constant Allelic Alteration On Chromosome 16p (TSC2 Gene) in Perivascular Epithelioid Cell Tumour (PEComa): Genetic Evidence for the Relationship of PEComa With Angiomyolipoma. J Pathol. 2008;214(3):387-93. PubMed PMID: 18085521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. AU - Pan,C-C, AU - Chung,M-Y, AU - Ng,K-F, AU - Liu,C-Y, AU - Wang,J-S, AU - Chai,C-Y, AU - Huang,S-H, AU - Chen,P C-H, AU - Ho,D M T, PY - 2007/12/19/pubmed PY - 2008/3/26/medline PY - 2007/12/19/entrez SP - 387 EP - 93 JF - The Journal of pathology JO - J. Pathol. VL - 214 IS - 3 N2 - Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/18085521/Constant_allelic_alteration_on_chromosome_16p__TSC2_gene__in_perivascular_epithelioid_cell_tumour__PEComa_:_genetic_evidence_for_the_relationship_of_PEComa_with_angiomyolipoma_ L2 - https://doi.org/10.1002/path.2289 DB - PRIME DP - Unbound Medicine ER -