Molecular characterization of an inherited ring (19) demonstrating ring opening.

Ring chromosomes arise following breakage in both chromosome arms and rejoining of the centric segment at the broken ends or by end-to-end fusion of the telomeres. The phenotype of ring carriers is unpredictable, and developmental abnormalities may occur even when the ring appears to be structurally balanced. This is believed to be due to mitotic instability from abnormal segregation and sister chromatid exchange in somatic cells. Although ring chromosomes usually arise as de novo events, transmittal from mosaic carriers to offspring sometimes occurs. In such cases, offspring with ring mosaicism in combination with a normal cell line remain unexplained. In this report, we used detailed molecular and cytogenetic analyses of a prenatally detected, inherited ring (19) to observe the behavior of the ring chromosome in culture, and to investigate the mechanism of inherited ring chromosome mosaicism.

Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By comparative genomic hybridization, spectral karyotyping, and expression array analysis.

BACKGROUND: A combination of molecular cytogenetic and expression array analysis has been performed on head and neck squamous cell carcinoma (HNSCC) of the oral cavity and supraglottis. These studies were performed to identify consensus regions of chromosomal imbalance and structural rearrangement to determine whether genes located in these genomic regions are subject to alterations in gene expression. Such combinatorial studies may help to identify recurrent patterns of altered gene expression in the context of specific chromosomal changes. METHODS: Comparative genomic hybridization (CGH) was used to identify net genomic imbalances and spectral karyotyping (SKY) to visualize the numerical and structural chromosomal changes in metaphase preparations. Expression microarray analysis of HNSCC cell lines and primary tongue tumors was also performed to identify genes that were commonly overexpressed or underexpressed compared with adjacent normal tissue. RESULTS: CGH detected gains at 3q (64%), 8q (45%) and 6q22-qter (45%) and losses at 18q22-qter (27%). SKY analysis of seven cell lines identified frequent structural rearrangement of the following chromosomal regions: 3q, 5p13-q11.2, 5q32-q34, 7p12-q11.2, 8p12-q12, 9p, 10p, 13p13-q12, 14q11.1-q11.2, 15p13-q11.2, 16p11.1-q11.1, 18q22-q23, and 22p13-q11.2. Consistent deregulation of interleukin 8, integrin alpha-6, c-MYC, epithelial discoidin domain receptor 1, and sterol regulatory element binding protein were apparent by expression analysis. Interestingly, some of these genes map to regions of genomic imbalance and chromosomal rearrangement as determined by our molecular cytogenetic analysis. CONCLUSIONS: In this small study, a combinatorial analysis using SKY, CGH, and microarray provides a model linking the changes in gene expression to changes in chromosomal dosage and structure. This approach has identified a subset of genetic changes that provide new opportunities for investigating the genetic basis of tumorigenesis in HNSCC.