Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi: Laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi

Maitra, Anirban; Gazdar, Adi F.; Moore, Todd O.; Moore, Angela

doi:10.1053/hupa.2002.31297

Cited by 44 publications

(20 citation statements)

References 28 publications

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“…When focal LOH was also taken into account (Table 3), the same four chromosome arms showed the highest overall frequencies of LOH (49-72%) in keeping with previous reports (e.g., refs. 3,[26][27][28][29][30][31][32][33][34]. Overall LOH was next most common (>40%) on 6q, 11q, and 17p, once again, in support of prior studies (e.g., refs.…”

Section: Discussionsupporting

confidence: 75%

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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: 75%

“…Overall LOH was next most common (>40%) on 6q, 11q, and 17p, once again, in support of prior studies (e.g., refs. 3,30,31,[34][35][36]. Additionally, we observed 33% LOH on 5q, a chromosome not previously associated with harboring a putative TSG for melanoma.…”

Section: Discussionmentioning

confidence: 73%

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

2007

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“…This is not significantly different from the 16 -43% previously detected at 1p36 (Walker et al, 1995;Bogdan et al, 2001;Maitra et al, 2002). The background/random LOH from our previous miniallelotype report on melanoma was on the order of 0 -17% (Walker et al, 1995).…”

Section: Discussioncontrasting

confidence: 44%

“…In the earliest report (Dracopoli et al, 1989), loss of alleles for markers on 1p was detected in 43% of melanoma biopsies and 52% of cell lines. Subsequent studies found a relatively low rate of allelic loss within the 1p36 region in melanomas, ranging from 13% (Maitra et al, 2002) to 16% (Bogdan et al, 2001) and 22% (Walker et al, 1995). Deletions of the 1p36 region are also prevalent in other tumors (Bello et al, 2000;Benn et al, 2000;Mora et al, 2000;Sun et al, 2001), including pheochromocytomas, parathyroid adenomas, hepatocellular car-cinomas, meningiomas, and neuroblastomas.…”

Section: Introductionmentioning

confidence: 93%

Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9‐mb interval

Walker

Indsto

Sood

et al. 2004

Genes Chromosomes & Cancer

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Loss of the short arm of chromosome 1 is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band 1p22. Critical recombinants in linked families localized the gene to a 15-Mb region between D1S430 and D1S2664. To map the locus more finely we have performed studies to assess allelic loss across the region in a panel of melanomas from 1p22-linked families, sporadic melanomas, and melanoma cell lines. Eighty percent of familial melanomas exhibited loss of heterozygosity (LOH) within the region, with a smallest region of overlapping deletions (SRO) of 9 Mb between D1S207 and D1S435. This high frequency of LOH makes it very likely that the susceptibility locus is a tumor suppressor. In sporadic tumors, four SROs were defined. SRO1 and SRO2 map within the critical recombinant and familial tumor region, indicating that one or the other is likely to harbor the susceptibility gene. However, SRO3 may also be significant because it overlaps with the markers with the highest 2-point LOD score (D1S2776), part of the linkage recombinant region, and the critical region defined in mesothelioma. The candidate genes PRKCL2 and GTF2B, within SRO2, and TGFBR3, CDC7, and EVI5, in a broad region encompassing SRO3, were screened in 1p22-linked melanoma kindreds, but no coding mutations were detected. Allelic loss in melanoma cell lines was significantly less frequent than in fresh tumors, indicating that this gene may not be involved late in progression, such as in overriding cellular senescence, necessary for the propagation of melanoma cells in culture.

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“…These functional roles, and the finding that human PTPRK gene has been mapped to the putative tumor suppressor gene region 6q22.2-q22.3 (26), which is frequently deleted in melanomas (27,28), overall support the hypothesis that loss of expression (29) as well as mutations occurring in functional domains of the PTPRK protein could directly affect the phenotype of normal growing cells and could play a role in tumor transformation and progression.…”

Section: Discussionmentioning

confidence: 57%

Identification of a Mutated Receptor-Like Protein Tyrosine Phosphatase κ as a Novel, Class II HLA-Restricted Melanoma Antigen

Novellino¹,

Renkvist²,

Rini³

et al. 2003

The Journal of Immunology

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Recent studies increasingly point to a pivotal role of CD4+ T cells in human anti-tumor immune response. Here we show that lymphocytes purified from a tumor-infiltrated lymph node of a melanoma patient that had remained disease free for 10 years after surgical resection of a lymph node metastasis comprised oligoclonal class II HLA-restricted CD4+ T cells recognizing the autologous tumor cells in vitro. In fact, the CD4+ T cell clones isolated from these lymphocytes displayed a tumor-specific, cytotoxic activity in addition to a Th1-like cytokine profile. By a genetic approach, a peptide derived from a mutated receptor-like protein tyrosine phosphatase κ was identified as a novel HLA-DR10-restricted epitope for all the melanoma-specific CD4+ T cell clones. The immunogenic peptide was shown to contain the mutated residue that was crucial for T cell recognition and activation. Moreover, a systemic immunity against the mutated peptide was detectable in the patient’s peripheral blood T lymphocytes obtained during the disease-free period of follow-up. These findings further support the relevance of CD4+ T cells directed against mutated epitopes in tumor immunity and provide the rationale for a possible usage of mutated, tumor-specific Ags for immunotherapy of human cancer.

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Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi: Laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi

Cited by 44 publications

References 28 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

Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9‐mb interval

Identification of a Mutated Receptor-Like Protein Tyrosine Phosphatase κ as a Novel, Class II HLA-Restricted Melanoma Antigen

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