Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

Journal

NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193

Informations de publication

Date de publication:
27 Mar 2024
Historique:
received: 08 08 2023
accepted: 13 03 2024
medline: 28 3 2024
pubmed: 28 3 2024
entrez: 28 3 2024
Statut: epublish

Résumé

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Identifiants

DOI: 10.1038/s41525-024-00405-z PMID: 38538628
pubmed: 38538628
doi: 10.1038/s41525-024-00405-z
pii: 10.1038/s41525-024-00405-z
doi:

Types de publication

Journal Article

Langues

eng

Pagination

24

Informations de copyright

© 2024. The Author(s).

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Auteurs

K M Ingley (KM)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Department of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Oncology, Royal Children's Hospital, Melbourne and Victorian Adolescent & Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Australia.
ORCID: 0000-0002-1806-2686

M Zatzman (M)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0000-0001-5235-4116

A M Fontebasso (AM)

Division of General Surgery, Sinai Health System, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

W Lo (W)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

V Subasri (V)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-6584-877X

A Goldenberg (A)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Computer Science, University of Toronto, Toronto, ON, Canada.

Y Li (Y)

Department of Pediatric and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

S Davidson (S)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Pediatric and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

N Kanwar (N)

Department of Pediatric and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

L Waldman (L)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Genetic Counselling, The Hospital for Sick Children, Toronto, ON, Canada.

L Brunga (L)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.

Y Babichev (Y)

Division of General Surgery, Sinai Health System, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

E G Demicco (EG)

Department of Pathology and Laboratory Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada.

A Gupta (A)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Department of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

M Szybowska (M)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Fred A. Litwin Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada.

S Thipphavong (S)

Department of Radiology, Sinai Health System, University of Toronto, Toronto, ON, Canada.

D Malkin (D)

Department of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

A Villani (A)

Department of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

A Shlien (A)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Pediatric and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0000-0002-0368-5370

R A Gladdy (RA)

Division of General Surgery, Sinai Health System, Department of Surgery, University of Toronto, Toronto, ON, Canada. rebecca.gladdy@sinaihealth.ca.
Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada. rebecca.gladdy@sinaihealth.ca.

R H Kim (RH)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Fred A. Litwin Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada. Raymond.kim@uhn.ca.
Department of Medicine, University of Toronto, Toronto, ON, Canada. Raymond.kim@uhn.ca.
ORCID: 0000-0002-2147-8674

Classifications MeSH