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.
Institute of Medical Biology, Singapore, Singapore. ruhe@u3pharma.com
Jens E
JE
Ruhe
Sylvia
S
Streit
Stefan
S
Hart
Chee-Hong
CH
Wong
Katja
K
Specht
Pjotr
P
Knyazev
Tatjana
T
Knyazeva
Liang Seah
LS
Tay
Hooi Linn
HL
Loo
Priscilla
P
Foo
Winnie
W
Wong
Sharon
S
Pok
Shu Jing
SJ
Lim
Huimin
H
Ong
Ming
M
Luo
Han Kiat
HK
Ho
Kaitian
K
Peng
Tze Chuen
TC
Lee
Martin
M
Bezler
Christian
C
Mann
Silvia
S
Gaertner
Heinz
H
Hoefler
Stefano
S
Iacobelli
Stephan
S
Peter
Alice
A
Tay
Sydney
S
Brenner
Byrappa
B
Venkatesh
Axel
A
Ullrich
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