Microarray‐based CGH of sporadic and syndrome‐related pheochromocytomas using a 0.1–0.2 Mb bacterial artificial chromosome array spanning chromosome arm 1p

Aarts, Marieke; Dannenberg, Hilde; deLeeuw, Ronald J.; Nederveen, Francien H. van; Verhofstad, A.A.J.; Lenders, Jacques W.M.; Dinjens, Winand N.M.; Speel, Ernst J. M.; Lam, Wan L.; Krijger, Ronald R. de

doi:10.1002/gcc.20268

Cited by 34 publications

(29 citation statements)

References 52 publications

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“…Moreover, most PCC in our study (22/36) had loss of the entire short arm of chromosome 1, by contrast to our previous study, where we found regional 1p loss in half of the cases (Aarts et al 2006). We speculate that the observed difference with our own previous studies and with series from others is related to the composition of the study group, which in the only present study comprised sporadic cases.…”

Section: Discussioncontrasting

confidence: 99%

“…We speculate that the observed difference with our own previous studies and with series from others is related to the composition of the study group, which in the only present study comprised sporadic cases. In the few cases with partial loss, no minimal region of common loss could be determined, preventing us to speculate on the presence of one region harboring tumor suppressor genes on 1p, which have been postulated by various authors (Geli et al 2005, Aarts et al 2006. Still, based on the high frequency of 1p loss in PCC, we support the idea of one or more tumor suppressor genes on this chromosome arm.…”

Section: Discussionmentioning

confidence: 48%

“…A similar array-CGH analysis has been performed on chromosome arm 1p, with 24 samples from hereditary and sporadic PCC, in which breakpoints of chromosome 1p could be identified precisely. These studies illustrate important differences between conventional and array-CGH (Aarts et al 2006). To further clarify the pathogenesis of sporadic PCC, we analyzed 36 sporadic benign PCC using a tiling array consisting of 32 433 BAC clones.…”

Section: Introductionmentioning

confidence: 99%

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Array-comparative genomic hybridization in sporadic benign pheochromocytomas

Nederveen¹,

Korpershoek²,

deLeeuw³

et al. 2009

Endocrine-Related Cancer

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Pheochromocytomas (PCC) are catecholamine-producing tumors arising from the adrenal medulla that occur either sporadically or in the context of hereditary cancer syndromes, such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease (VHL), neurofibromatosis type 1, and the PCC-paraganglioma syndrome. Conventional comparative genomic hybridization studies have shown loss of 1p and 3q in the majority of sporadic and MEN2-related PCC, and 3p and 11p loss in VHL-related PCC. The development of a submegabase tiling resolution array enabled us to perform a genome-wide high-resolution analysis of 36 sporadic benign PCC. The results show that there are two distinct patterns of abnormalities in these sporadic PCC, one consisting of loss of 1p with or without concomitant 3q loss in 20/36 cases (56%), the other characterized by loss of 3p with or without concomitant 11p loss in 11/36 (31%). In addition, we found loss of chromosome 22q at high frequency (35%), as well as the novel finding of high frequency chromosome 21q loss (21%). We conclude that there appear to be two subgroups of benign sporadic PCC, one of which has a pattern of chromosomal abnormalities that is comparable with PCC from patients with MEN2 and the other that is comparable with the PCC that arise in patients with VHL disease. In addition, genes on 21q and 22q might play a more important role in PCC pathogenesis than had been assumed thus far.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

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Array-comparative genomic hybridization in sporadic benign pheochromocytomas

Nederveen¹,

Korpershoek²,

deLeeuw³

et al. 2009

Endocrine-Related Cancer

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“…On the other hand, frequencies of primary OSCC cases, in which down-regulation of miR-137 and miR-193a expression was consistent with tumorspecific hypermethylation around these genes, were relatively high, similar to results in OSCC cell lines. miR-137 is located in chromosomal region 1p21.3, and loss of heterozygosity (LOH) in this region has been reported in meningioma (32), pheochromocytomas (33), and paraganglioma (34). LOH at 17q11.2, where miR-193a is located, has also been described in Barrett's esophageal tumors (35), neurofibromatosis 1 (36), ovarian adenocarcinoma (37), cervical carcinoma (38), and breast cancer (39).…”

Section: Discussionmentioning

confidence: 99%

Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer

et al. 2008

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In the last few years, microRNAs (miRNA) have started a revolution in molecular biology and emerged as key players in the carcinogenesis. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature that was specific for oral squamous cell carcinoma (OSCC), we first examined expression profiles of 148 miRNAs in a panel of 18 OSCC cell lines and the immortalized oral keratinocyte line RT7 as a control. Compared with RT7, the expression of 54 miRNAs (36.5%) was frequently downregulated in OSCC lines (<0.5-fold expression, z66.7% of 18 lines). Among these 54 miRNAs, we further analyzed four of these miRNAs (i.e., miR-34b, miR-137, miR-193a, and miR-203), located around CpG islands, to identify tumor-suppressive miRNAs silenced through aberrant DNA methylation. The expression of those four genes was restored by treatment with 5-aza-2 ¶-deoxycytidine in OSCC cells lacking their expression. In addition, expression levels of the four miRNAs were inversely correlated with their DNA methylation status in the OSCC lines. In primary tumors of OSCC with paired normal oral mucosa, down-regulation of miRNA expression through tumor-specific hypermethylation was more frequently observed for miR-137 and miR-193a than for miR-34b and miR-203. Moreover, the ectopic transfection of miR-137 or miR-193a into OSCC lines lacking their expressions significantly reduced cell growth, with down-regulation of the translation of cyclin-dependent kinase 6 or E2F transcription factor 6, respectively. Taken together, our results clearly show that miR-137 and miR-193a are tumor suppressor miRNAs epigenetically silenced during oral carcinogenesis. [Cancer Res 2008;68(7):2094-105]

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“…Loss of heterozygosity (LOH) and metaphase/array comparative genomic hybridization (CGH) studies have reported loss of chromosome arms 1p, 3p/q, 11p/q, 17p and 22q as frequent events in pheochromocytomas, indicating the potential presence of tumour suppressor genes on these autosomes. Gain of chromosomal material has appeared less frequently, and the most commonly affected chromosomal regions include 1q, 12q, 17q, 19p/q and 20q (Bender et al 2000, Edstrom et al 2000, August et al 2004, Cascon et al 2005, Jarbo et al 2006, Aarts et al 2006, van Nederveen et al 2009). Here, we have used a high-resolution whole-genome tiling array, consisting of more than 32 000 BAC (bacterial artificial chromosome) clones (32K array), to comprehensively characterize the DNA copy number status of 44 adrenal pheochromocytomas and 9 sympathetic paragangliomas.…”

Section: Introductionmentioning

confidence: 99%

Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

Sandgren

Ståhl²,

Andersson³

et al. 2010

Endocrine-Related Cancer

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Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (R32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (R14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.

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Microarray‐based CGH of sporadic and syndrome‐related pheochromocytomas using a 0.1–0.2 Mb bacterial artificial chromosome array spanning chromosome arm 1p

Cited by 34 publications

References 52 publications

Array-comparative genomic hybridization in sporadic benign pheochromocytomas

Array-comparative genomic hybridization in sporadic benign pheochromocytomas

Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer

Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

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