Traditionally, somatic mutations are detected by examining DNA sequence.
The fact that PAK mutations are detected in multiple tumor tissues makes PAKs a novel therapeutic drug target.
Most COL3A1 mutations are detected by using total RNA from patient-derived fibroblasts, which requires an invasive skin biopsy.
In addition, there is the report that 45%% of MSH2 mutations are detected in multiplex ligation-dependent probe amplification (MLPA) [11].
Mutations in candidate genes can explain a high proportion of FH cases, but for many, no causative mutations are detected (designed non-FG-GH), suggesting the existence of additional genetic variants associated with the disease.
Mutations are detected in between 50 and 80% of cases; those without a mutation often have higher triglyceride levels and may in fact have other causes for their high cholesterol, such as combined hyperlipidemia due to metabolic syndrome.
However, BRAF mutations are detected only in 1 2% of lung cancer patients.
A limitation of hotspot analysis is, by definition, that only the hotspot mutations are detected, while Sanger sequencing can identify all mutations in the PCR amplicon.
Here we describe a situation where the balance of these two factors is such that not one, but many, somatic mutations are detected.
For instance, K-ras mutations are detected in 20 30% of adenocarcinomas and inactivation of tumor suppressor genes, such as p53, p16INK4a, and Rb are frequently observed as well [2], [3], [4], [5].
While EGFR and KRAS mutations are detected in ∼10% and 20% of NSCLCs, respectively, somatic mutations have also been identified in HER2/ERBB2 (∼2%; exons 19 and 20) [12], [12] and HER4 (∼2%, exons 20, 23) [13], the lipid kinase PIK3CA (∼4%; exon 9) [14], and the serine/threonine kinase BRAF (∼2%; exons 11 and 15) [15] [17].
