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Germline SDHB ‐inactivating mutation in gastric spindle cell sarcoma
Author(s) -
Heilig Christoph E.,
Horak Peter,
Lipka Daniel B.,
Mock Andreas,
Uhrig Sebastian,
Kreutzfeldt Simon,
Richter Susan,
Gieldon Laura,
Fröhlich Martina,
Hutter Barbara,
Hübschmann Daniel,
Teleanu Veronica,
Schmier JohannWilhelm,
Philipzen Johannes,
BeuthienBaumann Bettina,
Schröck Evelin,
Deimling Andreas,
Bauer Sebastian,
Heining Christoph,
Mechtersheimer Gunhild,
Stenzinger Albrecht,
Brors Benedikt,
Wardelmann Eva,
Glimm Hanno,
Hartmann Wolfgang,
Fröhling Stefan
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22876
Subject(s) - sdhb , gist , cancer research , germline mutation , biology , sarcoma , loss of heterozygosity , germline , stomach , gastrointestinal tract , sdhd , pathology , somatic cell , dna methylation , stromal cell , mutation , medicine , genetics , gene , gene expression , allele , biochemistry
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex ( SDH ) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB ‐inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40‐year‐old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non‐GIST sarcoma of the gastrointestinal tract.