Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions

Abstract

We have previously found that the borders of evolutionarily conserved chromosomal regions often coincide with tumor-associated deletion breakpoints within human 3p12-p22. Moreover, a detailed analysis of a frequently deleted region at 3p21.3 (CER1) showed associations between tumor breaks and gene duplications. We now report on the analysis of 54 chromosome 3 breaks by multipoint FISH (mpFISH) in 10 carcinoma-derived cell lines. The centromeric region was broken in five lines. In lines with highly complex karyotypes, breaks were clustered near known fragile sites, FRA3B, FRA3C, and FRA3D (three lines), and in two other regions: 3p12.3-p13 (∼75 Mb position) and 3q21.3-q22

Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia

“…SDs cover about 10% of the human genome and are involved in numerous genomic diseases or cancer (Bailey and Eichler, 2006;Sharp et al, 2006;Gibcus et al, 2007;Darai-Ramqvist et al, 2008;Gu et al, 2008;Mefford and Eichler, 2009). In this paper, the involvement of SDs was proposed to explain the recurrent t(9;22) translocation in CML and the genomic deletions that could accompany the rearrangement.…”

“…During the last few years, genome analyses have revealed the crucial role of segmental duplications (SDs) in triggering constitutional and also tumor chromosomal abnormalities (Sharp et al, 2006;Gibcus et al, 2007;Darai-Ramqvist et al, 2008;Gu et al, 2008;Mefford and Eichler, 2009). Several rearrangements have been described so far to explain the occurrence of genomic disorders: recurrent, sharing a common size and showing clustering of breakpoints inside the SDs, and nonrecurrent rearrangements, involving regions of different sizes and showing breakpoints scattering in large regions (Gu et al, 2008).…”

Nutrition, Histone Epigenetic Marks, and Disease

“…Secondly, retrotransposition events account for ~10 % of known spontaneous mutations in mice (Kazazian and Moran 1998;Smit 1999). Thirdly, retroelements are associated with break-prone segmental duplications in tumors (Darai-Ramqvist et al 2008). Finally, chromosomal instability caused by aberrant epigenetic marks and the insertion of retrotransposons lead to oncogene activation, tumor suppressor gene inactivation, and the disruption of essential genes (Check 2003;Eden et al 2003;Feinberg and Tycko 2004).…”

“…The production of viral particles, the frequency of retrotransposition events, and the number of chromosomal abnormalities increase when long terminal repeats are derepressed by biotin depletion or HLCS knockdown in cell cultures, humans, and Drosophila (Chew et al 2008). Retrotransposition events can also cause cancer (Check 2003;Darai-Ramqvist et al 2008;Eden et al 2003;Fan 2007;Feinberg and Tycko 2004;Kazazian and Moran 1998;Smit 1999). Thus, biotin deficiency may be a risk factor for cancer formation.…”

An Evolutionary Biology Approach to Understanding Neurological Disorders

“…On an evolutionary timescale, chromosome rearrangements have also played a key role in the divergence of species and differences in chromosomal arrangements between species (Drosophila 12 Genomes Consortium, 2007; Kehrer- Sawatzki & Cooper, 2007;Pevzner & Tesler, 2003;Peng et al, 2006). Furthermore, the evolutionary chromosome breakpoints and chromosome breakpoints found in diseases, including cancer and developmental disorders, overlap (Darai-Ramqvist et al, 2008;Lindsay et al, 2006;Murphy et al, 2005). Therefore, understanding the mechanisms of chromosome breakage and rearrangement is an active field of biological research.…”