Biomedical subjects

Mireille Van Gele

Publications and source records attributed to Mireille Van Gele.

6 recordsLinked to original sources

PubMed2004

Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Biomarkers, Tumor↗

PubMed2003

Application of laser capture microdissection in genetic analysis of neuroblastoma and neuroblastoma precursor cells.

Recently developed quantitative and high-throughput technologies that allow automated and rapid screening of the whole genome, transcriptome and proteome have revolutionized the field of cancer genetics. At the same time, new challenges are met, e.g. the need for improved data analysis and standardization of tumor sample handling. Even if these issues are resolved, an 'old' problem in genetic tumor analysis remains, i.e. contamination of tumor samples by stromal and surrounding normal cells. To overcome this obstacle, laser capture microdissection (LCM) has been developed in order to procure the cells of interest from stained tissue sections with retention of morphology. In this review we describe the possible down-stream applications of LCM in the genetic analysis of neuroblastoma (NB). Special focus is given to MYCN copy number determination using real-time quantitative polymerase chain reaction (Q-PCR), analysis of 1p-, 3p- and 11q-deletions using loss of heterozygosity analysis and Q-PCR expression analysis of microdissected normal neuroblast cells and NB cells.

DNA, Neoplasm↗

PubMed2003

Evidence for involvement of a tumor suppressor gene on 1p in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNST) are rare soft-tissue malignancies. The genetic basis of these tumors is still poorly understood. Cytogenetic analyses predominantly revealed complex karyotypes, precluding the identification of recurrent chromosomal changes. We report loss of 1p material in a near-diploid karyotype with few or no additional structural chromosome changes in two sporadic cases of MPNST, indicating an important role of 1p loss in MPNST development. In one of these two tumors, a distal 1p deletion (1p31.2 approximately pter) was detected suggesting involvement of a tumor suppressor gene located within this distal region of 1p. Further evidence for recurrent 1p loss in MPNST was obtained by interphase fluorescence in situ hybridization, which showed loss of 1p material in 3 out of 13 tumors. These findings together with data from the literature suggest that loss of a tumor suppressor gene located within distal 1p is implicated in the pathogenesis of MPNST.

Child↗

PubMed2002

Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor (Merkel) cells and Merkel cell carcinoma.

Merkel cells form part of the peripheral neuroendocrine system of the skin and act as mechanoreceptors in touch response. Merkel cell carcinoma (MCC) is a rare, aggressive disease with similarities to small cell lung cancer (SCLC), which is also of neuroendocrine origin. We previously identified a novel DNA binding protein complex specific for MCC suspension cell lines, termed Merkel nuclear factor (MNF) by its binding to the POU-IV family DNA binding consensus sequence. Here we report that MNF contains the POU-IV family member Brn-3c and that Brn-3c is expressed in normal Merkel cells. Additionally, Brn-3c protein reactivity is restricted to a subset of MCC biopsies and is not seen in biopsies revealing adherent, variant cell lines lacking neuroendocrine markers. Recently, proper development of murine Merkel cells was shown to require the proneural basic helix-loop-helix transcription factor, atonal family member, MATH1. We demonstrate a correlation between Brn-3c and HATH1 reactivity in MCC biopsies and cell lines with retention of neuroendocrine phenotype. In SCLC, the related basic helix-loop-helix transcription factor HASH1 is responsible for neuroendocrine phenotype, but HASH1 transcripts were not detected in MCC cell lines. We propose that HATH1 and Brn-3c may form a transcriptional hierarchy responsible for determining neuroendocrine phenotype in Merkel cells and that lack of Brn-3c and/or HATH1 in MCC may indicate a more aggressive disease requiring closer patient follow-up.

Basic Helix-Loop-Helix Proteins↗

PubMed2002

Combined karyotyping, CGH and M-FISH analysis allows detailed characterization of unidentified chromosomal rearrangements in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Cytogenetic studies have indicated that deletions and unbalanced translocations involving chromosome 1 short arm material occur in 40% of the investigated cases. Recurrent chromosomal imbalances detected by comparative genomic hybridization (CGH) analysis were loss of 3p, 10q, 13q and 17p and gains of 1q, 3q, 5p and 8q. In order to study genomic aberrations occurring in MCC in further detail, we combined karyotyping, CGH and multiplex-fluorescence in situ hybridization (M-FISH), a strategy that proved to be successful in the analysis of other malignancies. Analysis of 6 MCC cell lines and 1 MCC tumor revealed mostly near-diploid karyotypes with an average of 5 chromosomal rearrangements. The observed karyotypic changes were heterogeneous, with 3-27 breakpoints per case, leading to imbalance of the involved chromosomal regions that was confirmed by CGH. Chromosomal rearrangements involving the short arm of chromosome 1, the long arm of chromosome 3 and gain of 5p material were the most frequently observed abnormalities in our study. In keeping with previous observations, this series of MCCs showed no evidence for high-level amplification. We provid a detailed description of chromosomal translocations occurring in MCC that could be useful to direct future intensive investigation of these chromosomal regions.

Aged↗

PubMed2002

Localization of the 17q breakpoint of a constitutional 1;17 translocation in a patient with neuroblastoma within a 25-kb segment located between the ACCN1 and TLK2 genes and near the distal breakpoints of two microdeletions in neurofibromatosis type 1 patients.

We have constructed a 1.4-Mb P1 artificial chromosome/bacterial artificial chromosome (PAC/BAC) contig spanning the 17q breakpoint of a constitutional translocation t(1;17)(p36.2;q11.2) in a patient with neuroblastoma. Three 17q breakpoint-overlapping cosmids were identified and sequenced. No coding sequences were found in the immediate proximity of the 17q breakpoint. The PAC/BAC contig covers the region between the proximally located ACCN1 gene and the distally located TLK2 gene and SCYA chemokine gene cluster. The observation that the 17q breakpoint region could not be detected in any of the screened yeast artificial chromosome libraries and the localization of the 17q breakpoint in the vicinity of the distal breakpoints of two microdeletions in patients with neurofibromatosis type 1 suggest that this chromosomal region is genetically unstable and prone to rearrangements.

Central Nervous System Neoplasms↗