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identify new therapeutic strategies that make use of all available drugs. The devel-
opment of gene expression profi les that can predict response to commonly used
cytotoxic agents provides opportunities to better use these drugs, including their use
in combination with existing targeted therapies.
OnkoMatch Tumor Genotyping
OnkoMatch™ tumor genotyping (GenPath Oncology), based on PCR amplifi cation
followed by single base extension detection of hotspot mutations that have been
identifi ed as key driver mutations, provides a reliable and robust tumor genotyping
platform for detecting 68 mutations (including EGFR, BRAF and KRAS) across 14
oncogenes. It was developed at the Massachusetts General Hospital where SNaPshot
Multiplex System has been applied for genotyping tumors such as NSCLC and in
infl uencing treatment decisions as well as directing patients toward relevant clinical
trials ( Sequist et al. 2011 ).
Gene Expression Profi les Predict Chromosomal Instability in Tumors
Microscopic examination of tumor specimens cannot always predict a cancer’s
aggressiveness, leading to increased interest in molecular approaches to diagnosis.
A genetic profi le indicating chromosomal instability − an increased tendency to
develop chromosomal aberrations that are critical in cancer development − is predic-
tive of clinical outcome in a broad range of cancer types. Chromosomal instability
leads to a condition known as aneuploidy, in which chunks of DNA are either miss-
ing or duplicated. Abnormal expression levels of genes at the different chromo-
somal locations indirectly refl ect the degree of aneuploidy and thus the degree of
chromosomal instability.
A 25-gene signature of chromosomal instability has been identifi ed from specifi c
genes whose expression was consistently correlated with total functional aneu-
ploidy in several cancer types (Carter et al. 2006 ). This signature was a signifi cant
predictor of clinical outcomes in a variety of cancers (breast, lung, medulloblas-
toma, glioma, mesothelioma and lymphoma). It could also differentiate between
primary tumors and tumor metastases, and in grade 1 and grade 2 breast cancers,
distinguished the more aggressive cancer within each grade. Using gene expression
data from 18 previous studies of cancer, representing 6 cancer types, the authors
found that this genetic profi le, or signature, predicted poor clinical outcome in 12 of
the populations studied. The technique may form the basis of a diagnostic tool that
could be used in the clinic and also help in the search for cancer drugs that reduce
chromosomal instability. This approach would be useful for developing personal-
ized therapy of cancer.
10 Personalized Therapy of Cancer