MYC is the most frequently amplified oncogene and the elevated expression of its product, c-Myc, is associated with transformation and poor outcome in human cancers. Other Myc family oncogenes have also been shown to play roles in specific cancer types, including neuroblastoma with 25% MYCN amplification and small cell lung cancer with 10% MYCL1 amplification. Cancers of the colon and ovary have been variously reported to display Myc amplification or over-expression in 10-60 % of cases, however most studies focused on a single Myc family oncogene and the relationship of Myc gene aberration to patient outcome is poorly investigated. We first used quantitative PCR and Western blotting to assess Myc family oncogene aberration at the gene, transcript and protein levels in a panel of 32 cancer cells, representing the most comprehensive analysis of Myc in cell lines to date. Next, the methodologies validated in cell lines were used to assess the importance of the Myc genes in patient cohorts of 130 colorectal cancers and of 230 epithelial ovarian cancers (EOC) of serous or endometrioid histology in terms of their relationship to clinical outcome.
Amplification of MYC occurred in approximately 10% of either ovarian or colorectal cancers, while 20% of ovarian tumours showed MYCN amplification. In serous EOC, tumours expressing the highest levels (top 10%) of MYC were associated with shorter progression-free survival while high MYC expression were associated with shorter overall (p=0.034) and progression-free (p=0.024) survival in high grade tumours of endometrioid subtype. In colorectal tumours, the prognostic value of Myc gene expression depended on tumour sites, with high MYCL1 expression in rectal tumours (p=0.02) and low MYC expression in sigmoid tumours (p=0.022) associated with shorter survival. These results indicate the heterogeneity of expression of Myc family oncogenes in the tumours of colon and ovary and identify potential new avenues for targeted therapy within cancer subtypes.