Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development

Alterations of E-cadherin and β-catenin in gastric cancer

BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. METHODS: We studied the alterations of E-cadherin and β-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). RESULTS: A high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and β-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for β-catenin IHC. An association was found between reduced expression of E-cadherin and β-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype. CONCLUSION: Our results support the hypothesis that alterations of E-cadherin and β-catenin play a role in the initiation and progression of gastric cancer

Bone: Adamantinoma

Review on Bone: Adamantinoma, with data on clinics, and the genes involved

Dedifferentiated adamantinoma with revertant mesenchymal phenotype

A

Cytogenetic analysis of adamantinoma of long bones:Further indications for a common histogenesis with osteofibrous dysplasia

Five adamantinomas of long bones were cytogenetically characterized to investigate the role of chromosomal aberrations in their histogenesis, as well as a putative relationship between adamantinoma and osteofibrous dysplasia (OFD). Three tumors had a classic histologic subtype, with abundant epithelium. Two of them revealed trisomies 7, 8, 12, and 19, combined with a balanced translocation, t(10;22), with centromere breakpoints in one tumor. The third showed a karyotype 51, XY, +X, +7, +12, +19, +21. The fourth tumor, of OFD-like subtype, showed trisomies 7, 8, and a small marker chromosome in a low percentage of cells. The fifth tumor, also of OFD-like subtype, displayed only a few keratin-positive cells from the multiple tissue blocks investigated. This latter tumor revealed a clonal abnormality with a karyotype 46,XX,t(2;11)(p23;q14)inv(11)(p14q14), which was confirmed with fluorescence in situ hybridization (FISH), using chromosome-specific library probes and chromosome 12 locus-specific probes. The trisomies 7, 8, and 22 also were described in OFD, which suggests a common histogenesis of OFD and adamantinoma. Our findings further support the probability of clonal origin of OFD. The OFD-like component may be an integral element of adamantinoma, rather than a tissue reaction to epithelial tumor cells. (C) 1997 Elsevier Science Inc., 1997