The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development
Please always quote using this URN: urn:nbn:de:bvb:20-opus-257476
- Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germlineFamilial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.…
Author: | Michael MeirORCiD, Katja Maurus, Jochen Kuper, Mohammed Hankir, Eva Wardelmann, Andreas Rosenwald, Christoph-Thomas Germer, Armin Wiegering |
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URN: | urn:nbn:de:bvb:20-opus-257476 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) |
Medizinische Fakultät / Pathologisches Institut | |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Language: | English |
Parent Title (English): | Genes, Chromosomes & Cancer |
Year of Completion: | 2021 |
Volume: | 60 |
Issue: | 12 |
Pagenumber: | 827–832 |
Source: | Genes, Chromosomes & Cancer 2021, 60(12):827–832. DOI: 10.1002/gcc.22988 |
DOI: | https://doi.org/10.1002/gcc.22988 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | GIST; KIT; germline mutation; mastocytosis; seminoma |
Release Date: | 2022/03/30 |
Licence (German): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |