Mitotic stability of small supernumerary marker chromosomes: a study based on 93 immortalized cell lines.

Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines. Therefore, 93 selected sSMC cases were studied here for the presence of the corresponding marker chromosomes before and after Epstein-Barr virus-induced immortalization. The obtained results showed that dicentric inverted duplicated-shaped sSMC are by far more stable in vitro than monocentric centric minute- or ring-shaped sSMC. Simultaneously, a review of the literature revealed that a comparable shape-dependent mitotic stability can be found in vivo in sSMC carriers. Additionally, a possible impact of the age of the sSMC carrier on mitotic stability was found: sSMC cell lines established from patients between 10-20 years of age were predominantly mitotically unstable. The latter finding was independent of the sSMC shape. The present study shows that in vitro models can lead to new and exciting insights into the biology of this genetically and clinically heterogeneous patient group.

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature.

Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content. According to this study, in 60% of the cases the sSMC originated from chromosomes 14 or 15. Euchromatic imbalances were caused by the sSMC presence in 30% of the cases. Notably, in 53% of infertile sSMC carriers, the sSMC was parentally transmitted. As we found indications of an as yet unknown mechanism for the elimination of sSMC from the human gene pool, sSMC could also play a role in elucidating the process of chromosome gain and loss during evolution. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.