Comprehensive Analyses of White-Handed Gibbon Chromosomes Enables Access to 92 Evolutionary Conserved Breakpoints Compared to the Human Genome.

Gibbon species (Hylobatidae) impress with an unusually high number of numerical and structural chromosomal changes within the family itself as well as compared to other Hominoidea including humans. In former studies applying molecular cytogenetic methods, 86 evolutionary conserved breakpoints (ECBs) were reported in the white-handed gibbon (Hylobates lar, HLA) with respect to the human genome. To analyze those ECBs in more detail and also to achieve a better understanding of the fast karyotype evolution in Hylobatidae, molecular data for these regions are indispensably necessary. In the present study, we obtained whole chromosome-specific probes by microdissection of all 21 HLA autosomes and prepared them for aCGH. Locus-specific DNA probes were also used for further molecular cytogenetic characterization of selected regions. Thus, we could map 6 yet unreported ECBs in HLA with respect to the human genome. Additionally, in 26 of the 86 previously reported ECBs, the present approach enabled a more precise breakpoint mapping. Interestingly, a preferred localization of ECBs within segmental duplications, copy number variant regions, and fragile sites was observed.

Loss of chromosome 4 correlates with better long-term survival and lower relapse rate after R0-resection of colorectal liver metastases.

PURPOSE: Liver metastases are the major cause of cancer-related death in colorectal cancer patients with a tendency to recur in over 50 % of the cases even after curatively intended surgery. Prognosis after liver resection, however, can neither be based on macroscopic or light microscopic evaluation of the metastases nor on clinical data alone. This is a pilot study in order to determine a potential influence of chromosomal aberrations on overall survival and relapse rate after curative liver resection. METHODS: Twenty randomly selected cases (10 patients with a survival of more and 10 patients with a survival of less than 5 years after resection) were studied by array comparative genomic hybridization. RESULTS: The distributions concerning age, gender, stage and grading of primary tumor, percentage of patients with chemotherapy, number and distribution of the liver metastases, Nordlinger and Fong scores showed no differences between long- and short-term survivors and no correlation to any chromosomal aberration. However, the relapse rate of patients with (partial) monosomy 4 was lower and the long-time survival better than in the other patients. CONCLUSIONS: Loss of chromosome 4 in colorectal liver metastases seems not only to be associated with the progression of the primary tumor as reported in the literature, but also with the long-term survival and the cumulative relapse rate after complete resection of colorectal liver metastases.

Multicolor FISH methods in current clinical diagnostics.

Multicolor FISH (mFISH) assays are currently indispensable for a precise description of derivative chromosomes. Routine application of such techniques on human chromosomes started in 1996 with the simultaneous use of all 24 human whole-chromosome painting probes in multiplex-FISH and spectral karyotyping. Since then, multiple approaches for chromosomal differentiation based on multicolor-FISH (MFISH) assays have been developed. Predominantly, they are applied to characterize marker or derivative chromosomes identified in conventional banding analysis. Since the introduction of array-based comparative genomic hybridization (aCGH), mFISH is also applied to verify and further delineate aCGH-detected aberrations. For the latter, it is important to consider the fact that aCGH cannot detect or characterize balanced rearrangements, which are important to be resolved in detail in infertility diagnostics. In addition, mFISH is necessary to distinguish different imbalanced situations detectable in aCGH; small supernumerary marker chromosomes have to be differentiated from insertions or unbalanced translocations. This review presents an overview on the available mFISH methods and their applications in pre- and post-natal clinical genetics.