20q11.22

E2F-1,RBAP1,RBBP3,RBP3

In non-small cell lung carcinomas (NSCLCs) E2F1 is significantly increased due to aberrant pRB status. In these cases the elevated levels of E2F1 are positively associated with the tumour growth index whereas apoptosis is not influenced as deregulation of the P53-MDM2 regulatory loop is a common phenomenon in NSCLC. Breast, thyroid and pancreatic cancer, seem to follow this same scenario, where aberrations in the pRB pathway coupled with defective P53 status, enhance E2F1 levels promoting tumor growth. In all these cases, the higher levels of E2F1 are also correlated with poorer outcome. Nevertheless, in other cases, like colon cancer, and diffuse large B-cell lymphomas the more aggressive disease is linked to lower E2F1 expression, as E2F1 in these cases acts as an oncosuppressor, enhancing apoptosis. Likewise, in adenocarcinomas of Barrett oesophagus E2F1 expression is negatively associated with tumor progression and positively with patient survival. In the case of transitional cell bladder carcinomas (TCCs) the findings are controversial. In one series of invasive bladder tumors E2F1 seems to play a tumor suppressive role, while in another series of superficial low-grade TCCs E2F1 is positively correlated with proliferation, but not with apoptosis. This discrepancy seems to lie in the type of TCC examined and the molecular characteristics of the tissue.
The most usual genetic alteration of the E2F1 gene is amplification, as has been reported in several leukemic (e.g. the HEL human erythroleukemia cell line) and melanoma cell lines. The gene has also been found amplified in various esophageal, colorectal, cervical and ovarian cancers, as well as in lymph node metastases of melanoma, and is often linked to chromosome 20q gains in these entities. Importantly, in esophageal squamous cell carcinomas, the 20q gains and the amplification of the E2F1 gene are linked with greater aggressiveness and poorer prognosis.