Distinct chromosomal aberrations in sinonasal mucosal melanoma as detected by comparative genomic hybridization

Dijk, Marcory van; Sprenger, Sandra H.E.; Rombout, Paul; Marres, H.A.M.; Kaanders, Johannes H.A.M.; Jeuken, Judith; Ruiter, Dirk J.

doi:10.1002/gcc.10156

Cited by 54 publications

(30 citation statements)

References 26 publications

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“…We found the most common (z25%) whole chromosome arm copy number gains occurred for 7p, 20q, and 22q (Table 2). This concurs with the conventional chromosome CGH data for these chromosome arms in various melanoma subtypes (4)(5)(6)(7)39). Regional amplifications of KIT, MITF, BRAF, NRAS, HRAS, KRAS, MDM2, CDK4, CCND1, MYC, and PIK3CA have been reported in some melanomas.…”

Section: Discussionsupporting

confidence: 89%

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

2007

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Although a number of genes related to melanoma development have been identified through candidate gene screening approaches, few studies have attempted to conduct such analyses on a genome-wide scale. Here we use Illumina 317K whole-genome single-nucleotide polymorphism arrays to define a comprehensive allelotype of melanoma based on loss of heterozygosity (LOH) and copy number changes in a panel of 76 melanoma cell lines. In keeping with previous reports, we found frequent LOH on chromosome arms 9p (72%), 10p (55%), 10q (55%), 9q (49%), 6q (43%), 11q (43%), and 17p (41%). Tumor suppressor genes (TSGs) can be identified through homozygous deletion (HD). We detected 174 HDs, the most common of which targeted CDKN2A (n = 33). The second highest frequency of HD occurred in PTEN (n = 8), another well known melanoma TSG. HDs were also common for PTPRD (n = 7) and HDAC4 (n = 3), TSGs recently found to be mutated or deleted in other cancer types. Analysis of other HDs and regions of LOH that we have identified might lead to the characterization of further melanoma TSGs. We noted 197 regional amplifications, including some centered on the melanoma oncogenes MITF (n = 9), NRAS (n = 3), BRAF

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Section: Discussionsupporting

confidence: 89%

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

2007

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“…The notion that melanocytic tumorigenesis may target different genes in a sitespecific manner has found support in a limited number of studies. Van Dijk et al (13), for example, recently found that sinonasal mucosal melanomas display a consistent pattern of chromosomal abnormalities that are distinct from the pattern seen in cutaneous melanomas. Even so, mucosal melanomas have not received the scientific scrutiny of their cutaneous counterparts.…”

Section: Discussionmentioning

confidence: 99%

Exon 15 BRAF Mutations Are Uncommon in Melanomas Arising in Nonsun-Exposed Sites

Cohen¹,

Rosenbaum²,

Begum

et al. 2004

Clinical Cancer Research

131

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Purpose: An activating point mutation of the BRAF oncogene has been identified in a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in melanomas arising from the mucosa of head and neck is unknown.Experimental Design: We tested 17 malignant mucosal melanomas of the head and neck for the thymine (T)3adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using direct sequencing and a newly developed assay that uses a novel primer extension method (Mutector assay). We also tested 21 cutaneous melanomas, including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the vulvar skin.Results: The 1796T3 A mutation was detected in only 1 (6%) of the sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in 8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar melanomas.Conclusions: In contrast to cutaneous melanomas arising in sun-exposed sites, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF. This finding additionally supports the view that the various subtypes of melanoma are not equivalent and that distinct genetic alterations may underlie well recognized differences in risk factors and behavioral patterns. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new strategies are developed that target specific genetic alterations.

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“…Gene amplifications were found to be significantly more frequent in acral and mucosal melanomas than in melanomas from non-acral skin [3,12]. In addition to the site-specific differences in the degree of genomic instability, there is increasing evidence of distinct patterns of genetic alterations depending on the localization of the primary tumor [12,41].…”

Section: Introductionmentioning

confidence: 99%

Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization

Glatz-Krieger

Pache²,

Tapia

et al. 2006

Virchows Arch

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To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanomas.

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Distinct chromosomal aberrations in sinonasal mucosal melanoma as detected by comparative genomic hybridization

Cited by 54 publications

References 26 publications

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

Exon 15 BRAF Mutations Are Uncommon in Melanomas Arising in Nonsun-Exposed Sites

Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization

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