Abnormal Elongations of HOX Gene Clusters May Cause Cancer

Hox gene activation is crucial for normal development of most organisms. Because of its importance, in both development and disease, it is intensively studied. Up to now, molecular methods have been almost exclusively used in order to explore the underlying mechanisms in normal embryonic growth (Tarchini and Duboule, 2006; Tschopp et al., 2009). The clustering of Hox genes is of particular interest in the case of the vertebrates (Duboule, 2007). Using classical genetic methods, Lewis discovered the fundamental property of Hox gene collinearity (Lewis, 1978). According to this collinearity, the ordered Hox1, Hox2, Hox3, etc., genes along the telomeric (3) to the centromeric (5) direction on the chromosome are activated in the same order in the ontogenetic units along the Anterior (head)—Posterior (tail) A/P axis of the embryo. The main feature of Hox gene collinearity is its multiscalar nature: the compact size of an inactivated Hox cluster is about 150 nm whereas the linear size of an early (mouse) embryo is about 1mm. The two sizes differ bymore than 4 orders of magnitude therefore themolecular mechanisms alone are not adequate to describe all Hox cluster collinearity data. Physical laws are more suitable to interrelate phenomena and entities extending over so different spatial scales, as for example the electrons and the nucleus of an atom. In the simplest case of the hydrogen atom, the electron is located in an “electronic cloud” around the nucleus (a proton). The size of the “electron cloud” is more than 4 orders of magnitude greater compared to the size of the atomic nucleus. The Coulomb force keeps the electron on track around the nucleus while the long-range structure of this force covers the space in between. The aforementioned multiscalar physical example motivated the formulation of an alternative model, the biophysical model (BM), to explain the collinear transcription in the Hox gene clusters (Papageorgiou, 2001, 2006). A simple heuristic pulling force F was introduced depending on two factors N and P giving rise to the following equation: