Abnormal gene expression profiles in unaffected parents of patients with hereditary-type retinoblastoma
Journal
Cancer Research
Journal Volume
66
Journal Issue
7
Pages
3428-3433
Date Issued
2006
Date
2006
Author(s)
Chen, Xi
Yan, Hailing
Li, Chuan-Yuan
Mitchell, James B.
Nagasawa, Hatsumi
Wilson, Paul F.
Peng, Yuanlin
Fitzek, Markus M.
Bedford, Joel S.
Little, John B.
Abstract
The hereditary form of retinoblastoma (Rb) is associated with a germ line mutation in one RB allele and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. In an earlier study, we observed an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb. In at least four of these five families, there was no family history of Rb, indicating a new germ line mutation. We hypothesize that the increased parental cell sensitivity to radiation may reflect the presence of an as yet unrecognized genetic abnormality occurring in one or both parents of children with Rb. In the present study, we use DNA microarray technology to determine whether differences in gene expression profiles occurred in the unaffected parents of patients with hereditary Rb relative to normal individuals. Microarray analyses were validated by quantitative reverse transcription-PCR measurements. A distinct difference was observed in the patterns of gene expression between unaffected Rb parents and normal controls. By use of the prediction analysis for microarrays and principal component analysis methodologies, significant differences between the two groups were identified when as few as nine genes were analyzed. Further study of this phenomenon may offer a new insight into the genetic mechanisms of Rb and perhaps more broadly in cancer biology. ?2006 American Association for Cancer Research.
SDGs
Other Subjects
article; controlled study; DNA microarray; familial cancer; gene expression; human; human cell; priority journal; retinoblastoma; reverse transcription polymerase chain reaction; Adult; Child; Fibroblasts; Gene Expression Profiling; Germ-Line Mutation; Humans; Oligonucleotide Array Sequence Analysis; Parents; Radiation Tolerance; Retinal Neoplasms; Retinoblastoma; Reverse Transcriptase Polymerase Chain Reaction; RNA; Skin
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