Resequencing analysis of the human tyrosine kinase gene family in pancreatic cancer.
OBJECTIVE
Pancreatic cancer is one of the most intractable of cancers. However, the comprehensive view of somatic mutations in this tumor is far from clear. The tyrosine kinase (TK) gene family, which encodes important regulators of various signal transduction pathways, is one of the most frequently altered gene families in human cancer.


METHODS
To clarify the somatic mutation profile of TKs in pancreatic cancer, we performed a systematic screening of mutations in the kinase domains of all human TK genes (636 exons of 90 genes in total) in 11 pancreatic cancer cell lines and 29 microdissected primary tumors.


RESULTS
We identified 15 nonsynonymous alterations that included 9 DNA alterations in cell lines and 6 somatic mutations in primary tumors. In particular, we identified the previously reported pathogenic mutation of NTRK3 in a KRAS/BRAF wild-type tumor and 2 somatic mutations in the Src family of kinases (YES1 and LYN) that would be expected to cause structural changes.


CONCLUSIONS
Our genome-wide resequencing approach revealed novel oncogenic pathways in pancreatic cancers.
Kubo
Takashi
T
National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Kuroda
Yukie
Y
Kokubu
Akiko
A
Hosoda
Fumie
F
Arai
Yasuhito
Y
Hiraoka
Nobuyoshi
N
Hirohashi
Setsuo
S
Shibata
Tatsuhiro
T
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020812:Receptor, trkC / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D018631:ras Proteins / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D020812:Receptor, trkC; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins