Mutational analyses of multiple oncogenic pathways in intraductal papillary mucinous neoplasms of the pancreas.
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.
Schönleben
Frank
F
Department of Otolaryngology/Head and Neck Surgery, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Allendorf
John D
JD
Qiu
Wanglong
W
Li
Xiaojun
X
Ho
Daniel J
DJ
Ciau
Nancy T
NT
Fine
Robert L
RL
Chabot
John A
JA
Remotti
Helen E
HE
Su
Gloria H
GH
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human