| Gain of chromosomes
and amplification of genes are genetic hallmarks
of cancers. Given the alarming rise of number
of women diagnosed with lung cancer, we wish to
examine female lung cancer genome for novel amplified
genes, using a whole genome method termed “Representational
Oligonucleotide Microarray Analysis (ROMA)“
developed by Wigler and coworkers (Lucito et al.
2003). We will systematically catalog each event
of chromosomal gain with ROMA in 25 female primary
lung tumor DNA samples and will compare with data
already collected in ROMA analyses performed on
34 male primary lung tumor DNA samples, with the
ultimate goal of identifying novel causal genes
that drive the female-prone gene amplification
in lung cancer. In a pilot study involving four
female NSCLC tumors, two tumors were found to
contain an amplified region on the sex chromosome
X, in which a kinase gene is hypothesized to be
the target of amplification. We will further characterize
this kinase gene in the realm of lung cancer genetics.
Simultaneously, we will perform ROMA analyses
on female lung tumor samples to identify additional
amplified genes for further investigation. A clear
precedent of female-prone gene amplification event
is the target gene of Herceptin“ therapy
- the HER2 oncogene. HER2 gene is amplified in
approximately 25-30% of female breast cancer patients,
but is only gained very rarely (1-2%) in male
breast cancer patients (Barlund et al. 2004).
With novel female-prone lung cancer genes identified,
new windows of opportunities will be presented
for creating diagnostic methods and therapies
that are potentially more suitable for women with
lung cancer.
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