Promoter methylation precedes chromosomal alterations in colorectal cancer development.

Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis.

Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps), 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR.

High resolution microarray CGH and MLPA analysis for improved genotype/phenotype evaluation of two childhood genetic disorder cases: ring chromosome 19 and partial duplication 2q.

A detailed analysis of the constitutional chromosomal changes in two pediatric patients was performed using high resolution genetic analysis techniques, microarray comparative genomic hybridization (array CGH) and multiplex ligation-dependent probe amplification (MLPA) as well as FISH. The aim was to come to a more precise characterization of the genotype/phenotype relationship. Case 1 was a girl of 25 months, showing areas of hypopigmentation along the lines of Blaschko and no other developmental abnormality.

Genomic stability and functional activity may be lost in telomerase-transduced human CD8+ T lymphocytes.

To obtain the large amount of T cells required for adoptive immunotherapy in a clinical setting, T-cell lifespan extension by human telomerase reverse transcriptase (hTERT) transduction is of particular interest. However, constitutive expression of hTERT is associated with malignant transformation and thus warrants a detailed evaluation of the safety of hTERT-transduced T cells before clinical application. In view of this, we performed an extensive cytogenetic analysis of hTERT-transduced MART-1 (melanoma antigen recognized by T cell 1)-and human papillomavirus type 16 (HPV16) E7-specific human CD8+ cytotoxic T lymphocytes (CTLs), reactive against melanoma and cervical carcinoma, respectively.

Generation and molecular characterization of head and neck squamous cell lines of fanconi anemia patients.

Patients with Fanconi anemia (FA) are prone to develop malignancies at an early age. Besides hematologic malignancies, squamous cell carcinomas in the anogenital region and head and neck are also frequently found in these patients. The aim of this study was to generate a panel of head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts of FA HNSCC, and to characterize these cell lines in comparison with a panel of seven cell lines from patients with sporadic HNSCC.

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma.

We applied comparative genomic hybridization (CGH) to 46 breast carcinoma samples, collected from 1993 to 1995, in order to detect chromosome 1q gains and 16q losses and to define whether samples showing both these alterations had distinct biopathologic features and different clinical outcome. A total of 22 samples (48%) had simultaneous chromosome 1q gain and 16q loss, which was always associated with other genetic changes. In total, 23 samples had various chromosome imbalances (including chromosome 1q gain independent of chromosome 16q loss and vice versa) and one sample did not show detectable alterations.

Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha).

B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue.

In lymph node-negative invasive breast carcinomas, specific chromosomal aberrations are strongly associated with high mitotic activity and predict outcome more accurately than grade, tumour diameter, and oestrogen receptor.

The objectives of this study were to analyse whether specific chromosomal gains and losses in lymph node-negative breast cancer correlate with other features and to evaluate their prognostic value. Seventy-six lymph node-negative breast carcinomas (median follow-up 46 months; range 9-105 months) were used. Histological grade, tumour type, maximal tumour diameter, oestrogen/progesterone receptor (ER/PR), mitotic activity index (MAI), and mean nuclear area (MNA) were assessed.

Barrett's adenocarcinomas resemble adenocarcinomas of the gastric cardia in terms of chromosomal copy number changes, but relate to squamous cell carcinomas of the distal oesophagus with respect to the presence of high-level amplifications.

Three different cancers predominantly occur at the gastro-oesophageal junction: squamous cell carcinomas of the distal oesophagus, adenocarcinomas of the distal oesophagus (Barrett's carcinomas), and adenocarcinomas of the gastric cardia. The aim of the present study was to investigate how, and to what extent, Barrett's carcinoma differs from adenocarcinoma of the gastric cardia on the one hand and squamous cell carcinoma of the distal oesophagus on the other, with respect to chromosomal aberrations and related gene expression. The present study analysed 14 squamous cell carcinomas, 24 Barrett's carcinomas, and 16 carcinomas of the gastric cardia.

Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridization.

Despite intensive therapy, the survival of children with medulloblastoma remains disappointing. Moreover, children who survive are affected by serious long-term sequelae of treatment that impair their quality of life. In search of chromosomal aberrations indicative of sites involved in oncogenic transformation and in an attempt to find reliable prognostic markers, the authors analyzed 15 medulloblastomas by comparative genomic hybridization.