Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines.
Protein tyrosine kinases (PTKs) play a critical role in the manifestation of cancer cell properties, and respective signaling mechanisms have been studied extensively on immortalized tumor cells. To characterize and analyze commonly used cancer cell lines with regard to variations in the primary structure of all expressed PTKs, we conducted a cDNA-based sequence analysis of the entire tyrosine kinase transcriptome of 254 established tumor cell lines. The profiles of cell line intrinsic PTK transcript alterations and the evaluation of 155 identified polymorphisms and 234 somatic mutations are made available in a database designated "Tykiva" (tyrosine kinome variant). Tissue distribution analysis and/or the localization within defined protein domains indicate functional relevance of several genetic alterations. The cysteine replacement of the highly conserved Y367 residue in fibroblast growth factor receptor 4 or the Q26X nonsense mutation in the tumor-suppressor kinase CSK are examples, and may contribute to cell line-specific signaling characteristics and tumor progression. Moreover, known variants, such as epidermal growth factor receptor G719S, that were shown to mediate anticancer drug sensitivity could be detected in other than the previously reported tumor types. Our data therefore provide extensive system information for the design and interpretation of cell line-based cancer research, and may stimulate further investigations into broader clinical applications of current cancer therapeutics.
Ruhe
Jens E
JE
Institute of Medical Biology, Singapore, Singapore. ruhe@u3pharma.com
Streit
Sylvia
S
Hart
Stefan
S
Wong
Chee-Hong
CH
Specht
Katja
K
Knyazev
Pjotr
P
Knyazeva
Tatjana
T
Tay
Liang Seah
LS
Loo
Hooi Linn
HL
Foo
Priscilla
P
Wong
Winnie
W
Pok
Sharon
S
Lim
Shu Jing
SJ
Ong
Huimin
H
Luo
Ming
M
Ho
Han Kiat
HK
Peng
Kaitian
K
Lee
Tze Chuen
TC
Bezler
Martin
M
Mann
Christian
C
Gaertner
Silvia
S
Hoefler
Heinz
H
Iacobelli
Stefano
S
Peter
Stephan
S
Tay
Alice
A
Brenner
Sydney
S
Venkatesh
Byrappa
B
Ullrich
Axel
A
D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases