Investigation of radiosensitivity gene signatures in cancer cell lines.
Intrinsic radiosensitivity is an important factor underlying radiotherapy response, but there is no method for its routine assessment in human tumours. Gene signatures are currently being derived and some were previously generated by expression profiling the NCI-60 cell line panel. It was hypothesised that focusing on more homogeneous tumour types would be a better approach. Two cell line cohorts were used derived from cervix [n = 16] and head and neck [n = 11] cancers. Radiosensitivity was measured as surviving fraction following irradiation with 2 Gy (SF2) by clonogenic assay. Differential gene expression between radiosensitive and radioresistant cell lines (SF2</> median) was investigated using Affymetrix GeneChip Exon 1.0ST (cervix) or U133A Plus2 (head and neck) arrays. There were differences within cell line cohorts relating to tissue of origin reflected by expression of the stratified epithelial marker p63. Of 138 genes identified as being associated with SF2, only 2 (1.4%) were congruent between the cervix and head and neck carcinoma cell lines (MGST1 and TFPI), and these did not partition the published NCI-60 cell lines based on SF2. There was variable success in applying three published radiosensitivity signatures to our cohorts. One gene signature, originally trained on the NCI-60 cell lines, did partially separate sensitive and resistant cell lines in all three cell line datasets. The findings do not confirm our hypothesis but suggest that a common transcriptional signature can reflect the radiosensitivity of tumours of heterogeneous origins.
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom.
John S
JS
Hall
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom.
Rohan
R
Iype
Experimental Oncology Group, The University of Manchester, Manchester, United Kingdom ; Gray Institute for Radiation Oncology and Biology, The University of Oxford, Oxford, United Kingdom.
Joana
J
Senra
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom ; Applied Computational Biology and Bioinformatics Group, CRUK Manchester Institute, Manchester, United Kingdom.
Janet
J
Taylor
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom.
Lucile
L
Armenoult
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom.
Kenneth
K
Oguejiofor
Applied Computational Biology and Bioinformatics Group, CRUK Manchester Institute, Manchester, United Kingdom.
Yaoyong
Y
Li
Experimental Oncology Group, The University of Manchester, Manchester, United Kingdom.
Ian
I
Stratford
Immunology Group. CRUK Manchester Institute, Manchester, United Kingdom.
Peter L
PL
Stern
Cancer Bioscience, Astra Zeneca, Macclesfield, United Kingdom.
Mark J
MJ
O'Connor
Applied Computational Biology and Bioinformatics Group, CRUK Manchester Institute, Manchester, United Kingdom.
Crispin J
CJ
Miller
Translational Radiobiology Group, The University of Manchester, Manchester, United Kingdom.
Catharine M L
CM
West
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009928:Organ Specificity; D020543:Proteome; D040901:Proteomics; D011836:Radiation Tolerance / Q000235:genetics*; D015203:Reproducibility of Results; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014158:Transcription, Genetic; D059467:Transcriptome; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism
D020543:Proteome