Chapter 2 - University of British Columbia

gene dosage with gene expression analysis would be useful to discern the target gene(s) of a
given copy number alteration.
1.2.3 Loss of heterozygosity (LOH) and allelic imbalance
Loss of heterozygosity (LOH) is a common genetic event in cancer [53]. In the normal cell,
each somatic chromosome has two copies, with one copy (or allele) originiating from each
parent. Subsequently, in the tumor, a specific segment from one of the copies of the
chromosome is lost, resulting in loss of heterozygosity.
Frequent regions of LOH have also been identified in the lung cancer genome [54-58]. While
initial studies involved the use of microsatellite markers placed throughout the genome and
thus, the resolution of these changes were limited, the application of SNP arrays were able to
refine these areas into specific chromosome arms [45, 46]. In addition to advances in SNP
array technology, analysis approaches were also developed that increased the detection
sensitivity of regions of LOH / allelic imbalance [59-63]. Although most areas with altered gene
dosage will also be detected as LOH (in case of copy number loss) and allelic imbalance (in
case of copy number gain), there are also areas in the genome which exhibit LOH but no
change in copy number, termed copy neutral LOH or uniparental disomy. However, the role of
UPD in lung cancer is not well understood.
1.3 Somatic mutations in lung cancer
Somatic mutations have also shown to be important in cancer development. In addition,
mutational analysis is also used for screening purposes in high risk populations (e.g. BRCA1/2
and hereditary breast cancer) as well as criteria for receiving targeted chemotherapy (e.g.
EGFR mutation and EGFR inhibitors). Many studies have been undertaken to identify
mutations in genes involved with important cellular processes pertinent to the cancer phenotype
such as DNA repair and cellular proliferation and have successfully identified key genes to a
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