Inactivating Mutations of RB1 and TP53 Correlate With Sarcomatous Histomorphology and Metastasis/Recurrence in Gastrointestinal Stromal Tumors

Merten L, Agaimy A, Moskalev E, Giedl J, Kayser C, Geddert H, Schaefer IM, Cameron S, Werner M, Stroebel P, Hartmann A, Haller F (2016)

Publication Type: Journal article

Publication year: 2016

Journal

American Journal of Clinical Pathology J B Lippincott Co

Book Volume: 146

Pages Range: 718-726

Journal Issue: 6

DOI: 10.1093/ajcp/aqw193

Abstract

Loss-of-function mutations in TP53 and CDKN2A have been found at varying frequencies in gastrointestinal stromal tumors (GISTs), while no mutations of RB1 have been reported to date. The aim of the current study was to determine the mutation frequency of TP53, RB1, and CDKN2A in GISTs.A cohort of 83 primary untreated GISTs was analyzed for mutations in TP53, RB1, and CDKN2A by massive parallel sequencing. Tumors with mutations in TP53 and RB1 were analyzed by fluorescence in situ hybridization for the corresponding gene loci.Two GISTs harbored inactivating mutations in RB1, and two other GISTs displayed inactivating mutations in TP53 All four tumors were KIT mutant high-risk tumors with highly cellular sarcomatous histomorphology and variable combinations of plump spindle cells to epithelioid highly atypical cells and high mitotic activity. Three of these patients developed recurrent or metastatic disease, while the fourth patient showed tumor rupture intraoperatively. The combined overall frequency of TP53 and RB1 mutations was 13% considering high-risk or malignant GISTs.TP53 and RB1 mutations seem to be restricted to high-risk/malignant GISTs and occur at an equal although relatively low frequency.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Evgeny Moskalev Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

St. Vincentius-Kliniken / ViDia Kliniken DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Georg-August-Universität Göttingen DE Germany (DE) Harvard University US United States (USA) (US)

How to cite

APA:

Merten, L., Agaimy, A., Moskalev, E., Giedl, J., Kayser, C., Geddert, H.,... Haller, F. (2016). Inactivating Mutations of RB1 and TP53 Correlate With Sarcomatous Histomorphology and Metastasis/Recurrence in Gastrointestinal Stromal Tumors. American Journal of Clinical Pathology, 146(6), 718-726. https://doi.org/10.1093/ajcp/aqw193

MLA:

Merten, Larissa, et al. "Inactivating Mutations of RB1 and TP53 Correlate With Sarcomatous Histomorphology and Metastasis/Recurrence in Gastrointestinal Stromal Tumors." American Journal of Clinical Pathology 146.6 (2016): 718-726.

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