title: A radiation-induced gene expression signature as a tool to predict acute radiotherapy-induced adverse side effects.
abstract: The majority of patients tolerate radiotherapy well, but some of them suffer from severe side effects. To find genes possibly predictive for radiosensitivity, mRNA profiles were generated before and 6h after in vitro irradiation with 5Gy. We analyzed lymphocytes from four head and neck and eight breast cancer patients with strong acute radiation toxicity and from 12 matching normal reacting patients in a blind study. Expression was also measured in lymphocyte subpopulations and Epstein-Barr transformed lymphocytes. Radiation response in whole lymphocyte populations was most similar to that of B cells. In peripheral blood lymphocytes of all patients; 153 genes were identified which were statistically significantly altered by a fold change of more than 50% by irradiation. The signatures of radio-responsive genes differed tremendously between primary and transformed cells. Pathway analysis revealed genes involved in p53 signalling, cell cycle control and apoptosis in response to radiation in primary lymphocytes. In these cells, a set of 67 radiation-induced genes was identified capable of differentiating between severe radiosensitive and normal reacting patients. More than one third of such classifying genes belong to the group of apoptosis or cell cycle regulating genes. The classifying potential of the expression signature has now to be validated in further patient cohorts.
authors.affiliation: Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mayer
authors.forename: Odilia
authors.initials: O
authors.lastname: Popanda
authors.forename: Burkhard
authors.initials: B
authors.lastname: Greve
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fritz
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Friederike
authors.initials: F
authors.lastname: Eckardt-Schupp
authors.forename: Maria
authors.initials: M
authors.lastname: Gomolka
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Peter
authors.initials: P
authors.lastname: Schmezer
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000532:radiotherapy; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics / Q000532:radiotherapy; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction