Genomic structure and mutation screening of the E2F4 gene in human tumors.

E2F4, a member of the E2F family of transcription factors, is abundant in non-proliferating and differentiated cells where it plays an important role in the suppression of proliferation-associated genes. The E2F4 gene spans 6 kb and has 10 exons. It contains a serine (CAG) repeat tract in exon 7, which is unstable in gastrointestinal tumors. To further investigate a possible role of this gene in tumorigenesis we performed mutational analysis and expression studies in different tumors. Primary human tumor tissue of the stomach, colon, breast and lung (28), metastatic tumors of the colon (3) and small cell lung tumor cell lines (18) were screened for somatic mutations in the coding region of E2F4. No mutation was found. Microsatellite instability of the CAG repeat, however, was documented in primary stomach and colon tumors. Northern blot analysis revealed upregulated E2F4 transcript levels in tumor cell lines. Our data suggest that a direct involvement of E2F4 in tumorigenesis is unlikely, although increased E2F4 expression may be associated with human cancer. Copyright 2000 Wiley-Liss, Inc.