OBJECTIVE: There is much accumulated evidence that EGFR, HER2, and their downstream signaling pathway members such as KRAS, BRAF, and PIK3CA are strongly implicated in cancer development and progression. Recently, mutations in the kinase domains of EGFR and HER2, associated with increased sensitivity to tyrosine kinase inhibitors, have been described. METHODS: To evaluate the mutational status of these genes in intraductal papillary mucinous neoplasm (IPMN)/intraductal papillary mucinous carcinoma (IPMC), EGFR and HER2 were analyzed in 36 IPMN/IPMC, and the results were correlated to the mutational status of the KRAS, BRAF, and PIK3CA genes in the samples. RESULTS: Together, we identified 1 silent mutation of HER2, 17 (43%) KRAS mutations, 1 (2.7%) BRAF mutation, and 4 (11%) mutations of PIK3CA in the IPMN/IPMC samples. CONCLUSIONS: The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.
OBJECTIVE: There is much accumulated evidence that EGFR, HER2, and their downstream signaling pathway members such as KRAS, BRAF, and PIK3CA are strongly implicated in cancer development and progression. Recently, mutations in the kinase domains of EGFR and HER2, associated with increased sensitivity to tyrosine kinase inhibitors, have been described. METHODS: To evaluate the mutational status of these genes in intraductal papillary mucinous neoplasm (IPMN)/intraductal papillary mucinous carcinoma (IPMC), EGFR and HER2 were analyzed in 36 IPMN/IPMC, and the results were correlated to the mutational status of the KRAS, BRAF, and PIK3CA genes in the samples. RESULTS: Together, we identified 1 silent mutation of HER2, 17 (43%) KRAS mutations, 1 (2.7%) BRAF mutation, and 4 (11%) mutations of PIK3CA in the IPMN/IPMC samples. CONCLUSIONS: The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.
Authors: K Yamao; K Ohashi; T Nakamura; T Suzuki; Y Shimizu; Y Nakamura; Y Horibe; A Yanagisawa; A Nakao; Y Nimuara; Y Naito; T Hayakawa Journal: Hepatogastroenterology Date: 2000 Jul-Aug
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Authors: Suresh T Chari; Dhiraj Yadav; Thomas C Smyrk; Eugene P DiMagno; Laurence J Miller; Massimo Raimondo; Jonathan E Clain; Ian A Norton; Randall K Pearson; Bret T Petersen; Maurits J Wiersema; Michael B Farnell; Michael G Sarr Journal: Gastroenterology Date: 2002-11 Impact factor: 22.682
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Authors: F Maire; P Hammel; B Terris; F Paye; J-Y Scoazec; C Cellier; M Barthet; D O'Toole; P Rufat; C Partensky; E Cuillerier; P Lévy; J Belghiti; P Ruszniewski Journal: Gut Date: 2002-11 Impact factor: 23.059
Authors: Frank Schönleben; Wanglong Qiu; Karl C Bruckman; Nancy T Ciau; Xiaojun Li; Margaret H Lauerman; Harold Frucht; John A Chabot; John D Allendorf; Helen E Remotti; Gloria H Su Journal: Cancer Lett Date: 2006-11-09 Impact factor: 8.679
Authors: Thomas J Lynch; Daphne W Bell; Raffaella Sordella; Sarada Gurubhagavatula; Ross A Okimoto; Brian W Brannigan; Patricia L Harris; Sara M Haserlat; Jeffrey G Supko; Frank G Haluska; David N Louis; David C Christiani; Jeff Settleman; Daniel A Haber Journal: N Engl J Med Date: 2004-04-29 Impact factor: 91.245
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