Challenges in identifying candidate amplification targets in human cancers: chromosome 8q21 as a case study.
Detailed genomic characterization of cancer specimens is required to identify all genes whose dysregulation contributes to tumorigenesis and/or tumor progression. These include amplification target genes, whose oncogenic functions derive from their overexpression in response to increased gene copy number, and which increasingly serve as therapeutic targets and predictive markers. We propose that identifying novel amplification target genes is becoming more challenging, and may require the comparative analysis of multiple studies mapping gene copy number changes and/or defining associations between gene copy number and expression. We therefore reviewed the array comparative genomic hybridization and single nucleotide polymorphism profiling literature to identify copy number increases that were restricted to chromosome 8q21 in human cancers, which were reported most frequently in breast cancer. We determined the minimal regions of overlap between gained regions and then examined which chromosome 8q21 genes were most frequently overexpressed, or otherwise supported, in individual studies. As these combined approaches supported the previously proposed amplification targets TCEB1, TPD52, and WWP1, the comparison of multiple genomic studies may therefore effectively predict candidate gene amplification targets, and prioritize these for further study.
Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, Australia ; The University of Sydney Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, Westmead, Australia.
Jennifer A
JA
Byrne
Yuyan
Y
Chen
Nancy
N
Martin La Rotta
Gregory B
GB
Peters