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

K. M. Ingley; M. Zatzman; A. M. Fontebasso; W. Lo; V. Subasri; A. Goldenberg; Y. Li; S. Davidson; N. Kanwar; L. Waldman; L. Brunga; Y. Babichev; E. G. Demicco; A. Gupta; M. Szybowska; S. Thipphavong; D. Malkin; A. Villani; A. Shlien; R. A. Gladdy; R. H. Kim

doi:10.1038/s41525-024-00405-z

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

K. M. Ingley, M. Zatzman, A. M. Fontebasso, W. Lo, V. Subasri, A. Goldenberg, Y. Li, S. Davidson, N. Kanwar, L. Waldman, L. Brunga, Y. Babichev, E. G. Demicco, A. Gupta, M. Szybowska, S. Thipphavong, D. Malkin, A. Villani, A. Shlien, R. A. GladdyR. H. Kim

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	24
Journal	npj Genomic Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41525-024-00405-z
State	Published - 1 Dec 2024
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41525-024-00405-z

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Ingley, K. M., Zatzman, M., Fontebasso, A. M., Lo, W., Subasri, V., Goldenberg, A., Li, Y., Davidson, S., Kanwar, N., Waldman, L., Brunga, L., Babichev, Y., Demicco, E. G., Gupta, A., Szybowska, M., Thipphavong, S., Malkin, D., Villani, A., Shlien, A., ... Kim, R. H. (2024). Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib. npj Genomic Medicine, 9(1), Article 24. https://doi.org/10.1038/s41525-024-00405-z

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title = "Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib",

abstract = "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.",

author = "Ingley, \{K. M.\} and M. Zatzman and Fontebasso, \{A. M.\} and W. Lo and V. Subasri and A. Goldenberg and Y. Li and S. Davidson and N. Kanwar and L. Waldman and L. Brunga and Y. Babichev and Demicco, \{E. G.\} and A. Gupta and M. Szybowska and S. Thipphavong and D. Malkin and A. Villani and A. Shlien and Gladdy, \{R. A.\} and Kim, \{R. H.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

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doi = "10.1038/s41525-024-00405-z",

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Ingley, KM, Zatzman, M, Fontebasso, AM, Lo, W, Subasri, V, Goldenberg, A, Li, Y, Davidson, S, Kanwar, N, Waldman, L, Brunga, L, Babichev, Y, Demicco, EG, Gupta, A, Szybowska, M, Thipphavong, S, Malkin, D, Villani, A, Shlien, A, Gladdy, RA & Kim, RH 2024, 'Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib', npj Genomic Medicine, vol. 9, no. 1, 24. https://doi.org/10.1038/s41525-024-00405-z

TY - JOUR

T1 - Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib

AU - Ingley, K. M.

AU - Zatzman, M.

AU - Fontebasso, A. M.

AU - Lo, W.

AU - Subasri, V.

AU - Goldenberg, A.

AU - Li, Y.

AU - Davidson, S.

AU - Kanwar, N.

AU - Waldman, L.

AU - Brunga, L.

AU - Babichev, Y.

AU - Demicco, E. G.

AU - Gupta, A.

AU - Szybowska, M.

AU - Thipphavong, S.

AU - Malkin, D.

AU - Villani, A.

AU - Shlien, A.

AU - Gladdy, R. A.

AU - Kim, R. H.

PY - 2024/12/1

Y1 - 2024/12/1

N2 - 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.

AB - 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.

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SN - 2056-7944

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JO - npj Genomic Medicine

JF - npj Genomic Medicine

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ER -

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

Abstract

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UN SDGs

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