KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer.
We propose that 11p15 harbors two imprinted gene domains-a more centromeric domain including KVLQT1 and p57(KIP2), alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterations in which are more common in cancer.
Several lines of evidence support this hypothesis: (a) we have discovered a novel genetic alteration in cancer, loss of imprinting, which affects several of these genes, and is one of the most common genetic changes in human cancer; (b) we have found that the hereditary disorder Beckwith-Wiedemann syndrome, which predisposes to cancer and causes prenatal overgrowth, involves alterations in p57KIP2, IGF-II, H19, and KvLQT1; (c) we have found both genetic (somatic mutation in Wilms' tumor) and epigenetic alterations (DNA methylation) in cancer; and (d) we can partially reverse abnormal imprinting using an inhibitor of DNA methylation.