As previously pointed out, this reflects the limits of our prior technology. As discussed previously, homozygosity of tumor oncogenes in cancer cell lines is frequent, although the available information did not permit the distinction between MASI with CNGs or UPD as the mechanism. Using gene-specific and genome-wide approaches we found that UPD was frequent for three EGFR pathway genes, especially for KRAS gene. Relatively little data exists in the literature for KRAS CNGs in human tumors. Furthermore, KRAS homozygosity was observed independent of mutational status as previously described. The wild type allele of KRAS can also inhibit lung carcinogenesis in mice, providing a possible 20S-Notoginsenoside-R2 explanation for the frequent finding of UPD with mutant and wild type oncogenes. 
MASI has apparent biological and clinical significance. MASI at the genomic level was precisely maintained after transcription. While mutations, CNGs and allelic imbalance of mA and wA may all contribute to tumorigenesis, combinations of the three events may be more effective than any single event. Evidence for this concept was provided by our finding that the combination of mutation and CNGs acted synergistically to enhance ras GTPase activity. A recent report found that all KRAS mutations did not exert an equal effect on tumor cells. Cancer cell lines harboring KRAS mutations could be broadly divided into KRAS-dependent and KRAS-independent groups. The vast majority of KRAS-dependent lines exhibited focal KRAS CNGs, in contrast to KRAS-independent lines. This study provides further evidence that the combination of KRAS mutations and CNGs act synergistically. Our previous findings that EGFR mutations were associated with tumor initiation while EGFR CNG might be more regarded as a tumor progression event, provide further evidence of their co-operative role in tumorgenesis. Understanding the mechanism of MASI could elucidate new understandings of tumor biology and may contribute to the development of rational targeted therapies. MASI in its various forms is frequently present in mutant EGFR and KRAS tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, copy number gains and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration. Microarray gene expression data have been integrated to increase statistical power. Increasing sample size is a bottleneck in DNA microarray-based gene expression studies as microarray experiments are time consuming, expensive, noisy and limited to the number of biological samples. To circumvent this problem, microarray gene expression data sets addressing the same or similar biological questions have been analyzed jointly either by so-called meta analysis, which means integration at the level of results derived separately from individual data sets, or by data 4-(Benzyloxy)phenol merging. But data integration prior to analysis potentially faces problems related to reproducibility as different microarray platforms use different probes for the same genes and return expression values on different numerical scales. Some studies combined data sets generated with the same chip, or with the same technology platform but different chips, or with heterogeneous microarray technologies. The rationale behind combining data sets generated only from the same chip or platform was to avoid the cross-platform bias.