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The evolution of satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes in the Hominoidea superfamily is described. The results have demonstrated that each SatIII subfamily is an independent evolutionary unit, that the rate of evolution is not uniform between species and that the evolution within a species is not uniform between chromosomes.

Cell lines provide a good model for studies on molecular and cellular events accompanying neoplastic transformation and cancer progression. The data in recent literature suggest an occurrence of repetitive chromosome aberrations that can be linked with particular stages of cancer. Ten cell lines derived from squamous cell carcinoma of the larynx at the University of Turku were karyotyped. The studied cell lines represented a variety of primary locations of the tumors, TNM staging and histological grading. Karyotyping was done by the classical cytogenetic technique with the application of GTG, QFQ and other banding techniques; some complex aberrations were analyzed by the FISH technique. The results document several numerical and structural aberrations. Attention was focused on the monosomy of chromosomes 13, 17 and 18, frequent deletions of the Y chromosome. Structural aberrations were frequently seen at chromosomes 1, 3, 4, 7, 8, 9 and 11, mostly as deletions (usually deletions of a whole arm), translocations, isochromosomes, duplications and marker chromosomes. The study is in progress and aims to find a correlation between particular aberrations and disease staging. At present, two observations seem to be firm: the amplification of the 11q13 region appeared in tumors with a short survival. However, the primary location of the tumor should be taken into account when considering 11q13 as a prognostic marker. The same is applicable for del(9p), which indicates an early stage of disease. Besides the frequent chromosome aberrations, attention should be paid to marker chromosomes that are potentially specific for laryngeal cancer. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) associated genes [FANCA, -B, -C, FANCD1(BRCA2), -D2, -E, -F, -G, -I, -L, -M, FANCN (PALB2), FANCJ(BRIP1) and FA-linked BRCA1] encode proteins of DNA damage response pathways mutated in FA patients. FA is characterized by congenital malformations, chromosomal instability and high cancer susceptibility. FA patients have a 500-700 times higher risk of head and neck squamous cell carcinoma (HNSCC) compared to the non-FA population. As DNA methylation comprises one of the known gene inactivation mechanisms in cancer we have investigated the methylation status of 13 FA and one FA-linked gene in order to assess the role of FA in sporadic laryngeal squamous cell carcinoma (LSCC) tumor samples. Thirteen laryngeal squamous carcinoma cell lines (UT-SCC) and 64 primary laryngeal carcinoma cases were analyzed by bisulfite pyrosequencing. DNA from buccal swabs of 10 healthy volunteers was used as a control group. Promoter regions of FANCA, BRCA1 and BRCA2 displayed recurrent alterations in the methylation levels in cancer samples as compared to buccal swabs controls. For FANCA, hypomethylation was observed in 11/13 cell lines (p<0.0003) and all 64 primary larynx samples (p<0.001) compared to buccal swabs. For BRCA1, 4/13 cell lines (p=0.04) and 3/58 primary laryngeal cases (p=0.22) showed hypomethylation. In BRCA2, all 13 cell lines (p<0.0001) 4/63 primary LSCC (p<0.01) showed hypermethylation as compared to controls. In conclusion, we show recurrent alterations of DNA methylation levels in three Fanconi anemia genes which might contribute to the pathogenesis of LSCC.

Chromosomal abnormalities often result in the improper dosage of genes in a particular chromosome or chromosome segment, which may cause specific and complex clinical phenotypes. Comparative genomic hybridization by microarray (array CGH) is a high-throughput and high-resolution method for the detection of microscopic and submicroscopic chromosome abnormalities, some of which may not be detectable by conventional cytogenetic techniques. In addition, with the human genome sequenced and publicly available, array CGH allows for the direct correlation between chromosomal anomalies and genomic sequence. Properly constructed, microarrays have the potential to be a valuable tool for the detection of chromosomal abnormalities in cancer and genetic disease.

Numerical and structural chromosomal rearrangements, such as aneuploidies, deletions, duplications, and other aberrations have been associated with congenital abnormalities, pregnancy loss, and malignancy. Detection of these genetic changes is possible by cytogenetic analysis. The karyotype is determined by analysis of metaphase or prometaphase chromosomes of peripheral blood lymphocytes after banding procedures. This analysis plays an important role in determining patient diagnosis and care. In this chapter, we describe the basic approach of cytogenetic analysis: arresting the cell in metaphase or prometaphase, the obtaining of metaphase chromosome spreads, and staining and chromosome analysis.