Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs

J. F. Emile; S. Brahimi; J. M. Coindre; P. P. Bringuier; G. Monges; P. Samb; L. Doucet; I. Hostein; B. Landi; M. P. Buisine; A. Neuville; O. Bouché; P. Cervera; J. L. Pretet; J. Tisserand; A. Gauthier; A. Le Cesne; J. C. Sabourin; J. Y. Scoazec; S. Bonvalot; C. L. Corless; M. C. Heinrich; J. Y. Blay; P. Aegerter

doi:10.1007/s12032-011-0074-y

Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs

J. F. Emile, S. Brahimi, J. M. Coindre, P. P. Bringuier, G. Monges, P. Samb, L. Doucet, I. Hostein, B. Landi, M. P. Buisine, A. Neuville, O. Bouché, P. Cervera, J. L. Pretet, J. Tisserand, A. Gauthier, A. Le Cesne, J. C. Sabourin, J. Y. Scoazec, S. BonvalotC. L. Corless, M. C. Heinrich, J. Y. Blay, P. Aegerter

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Résumé

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502-503dup and KIT exon 11 557-559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

langue originale	Anglais
Pages (de - à)	1765-1772
Nombre de pages	8
journal	Medical Oncology
Volume	29
Numéro de publication	3
Les DOIs	https://doi.org/10.1007/s12032-011-0074-y
état	Publié - 1 sept. 2012

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10.1007/s12032-011-0074-y

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Emile, J. F., Brahimi, S., Coindre, J. M., Bringuier, P. P., Monges, G., Samb, P., Doucet, L., Hostein, I., Landi, B., Buisine, M. P., Neuville, A., Bouché, O., Cervera, P., Pretet, J. L., Tisserand, J., Gauthier, A., Le Cesne, A., Sabourin, J. C., Scoazec, J. Y., ... Aegerter, P. (2012). Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs. Medical Oncology, 29(3), 1765-1772. https://doi.org/10.1007/s12032-011-0074-y

@article{a8842735170d4f13a8b8aaa8b7f77e9f,

title = "Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs",

abstract = "Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502-503dup and KIT exon 11 557-559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.",

keywords = "Epidemiology, Gastrointestinal tumor, Sarcoma, Tyrosine kinase receptor",

author = "Emile, {J. F.} and S. Brahimi and Coindre, {J. M.} and Bringuier, {P. P.} and G. Monges and P. Samb and L. Doucet and I. Hostein and B. Landi and Buisine, {M. P.} and A. Neuville and O. Bouch{\'e} and P. Cervera and Pretet, {J. L.} and J. Tisserand and A. Gauthier and {Le Cesne}, A. and Sabourin, {J. C.} and Scoazec, {J. Y.} and S. Bonvalot and Corless, {C. L.} and Heinrich, {M. C.} and Blay, {J. Y.} and P. Aegerter",

note = "Funding Information: unrestricted grants from Novartis Pharma. The authors would like to thank patients who participated to MolecGIST study and their families, as well as all the pathologists, oncologists, surgeons, gastroenterologists, physicians and clinical research assistants who participated to the collection of the data. The list is available on http://www.gist-france.org/remerciements.html. Funding Information: Acknowledgments MolecGIST study was supported by grants from Ligue contre le Cancer, Institut National du Cancer (INCa) and",

year = "2012",

month = sep,

day = "1",

doi = "10.1007/s12032-011-0074-y",

language = "English",

volume = "29",

pages = "1765--1772",

journal = "Medical Oncology",

issn = "1357-0560",

number = "3",

}

Emile, JF, Brahimi, S, Coindre, JM, Bringuier, PP, Monges, G, Samb, P, Doucet, L, Hostein, I, Landi, B, Buisine, MP, Neuville, A, Bouché, O, Cervera, P, Pretet, JL, Tisserand, J, Gauthier, A, Le Cesne, A, Sabourin, JC, Scoazec, JY, Bonvalot, S, Corless, CL, Heinrich, MC, Blay, JY & Aegerter, P 2012, 'Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs', Medical Oncology, VOL. 29, Numéro 3, p. 1765-1772. https://doi.org/10.1007/s12032-011-0074-y

TY - JOUR

T1 - Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs

AU - Emile, J. F.

AU - Brahimi, S.

AU - Coindre, J. M.

AU - Bringuier, P. P.

AU - Monges, G.

AU - Samb, P.

AU - Doucet, L.

AU - Hostein, I.

AU - Landi, B.

AU - Buisine, M. P.

AU - Neuville, A.

AU - Bouché, O.

AU - Cervera, P.

AU - Pretet, J. L.

AU - Tisserand, J.

AU - Gauthier, A.

AU - Le Cesne, A.

AU - Sabourin, J. C.

AU - Scoazec, J. Y.

AU - Bonvalot, S.

AU - Corless, C. L.

AU - Heinrich, M. C.

AU - Blay, J. Y.

AU - Aegerter, P.

N1 - Funding Information: unrestricted grants from Novartis Pharma. The authors would like to thank patients who participated to MolecGIST study and their families, as well as all the pathologists, oncologists, surgeons, gastroenterologists, physicians and clinical research assistants who participated to the collection of the data. The list is available on http://www.gist-france.org/remerciements.html. Funding Information: Acknowledgments MolecGIST study was supported by grants from Ligue contre le Cancer, Institut National du Cancer (INCa) and

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502-503dup and KIT exon 11 557-559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

AB - Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502-503dup and KIT exon 11 557-559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

KW - Epidemiology

KW - Gastrointestinal tumor

KW - Sarcoma

KW - Tyrosine kinase receptor

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U2 - 10.1007/s12032-011-0074-y

DO - 10.1007/s12032-011-0074-y

M3 - Article

C2 - 21953054

AN - SCOPUS:84867300058

SN - 1357-0560

VL - 29

SP - 1765

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JO - Medical Oncology

JF - Medical Oncology

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