Criteria to define HLA haplotype loss in human solid tumors

Ramal, L.M.; Feenstra, Manita; Zwan, Anne Wil van der; Collado, Antonia; López–Nevot, Miguel A.; Tilanus, M.G.J.; Garrido, Federico

doi:10.1034/j.1399-0039.2000.550507.x

Cited by 40 publications

(27 citation statements)

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“…In this regard, Lehmann et al (51) demonstrated that the TAs recognized by the CTLs isolated from recurrent melanoma metastases were different from those recognized by the CTLs isolated from autologous primary lesions. In addition, some of us (14) have shown a shifting of CTL specificity from HLA-A2-MART-1 [27][28][29][30][31][32][33][34][35] complexes to HLA-A2-Tyr 369 -377 complexes in two sequential melanoma metastases with distinct HLA class I abnormalities caused by a mutant ␤ 2 m protein (32). These results are consistent with the possibility that the specificity of a patient's immune response can change in response to changes in the expression of targets by melanoma cells, which have developed immunoescape mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy

Chang

Pirozzi²,

Wen

et al. 2015

Journal of Biological Chemistry

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Background: Understanding the mechanism of tumor immune resistance can help design effective cancer immunotherapy. Results: A novel tapasin mutation, haplotype loss, and HLA epigenetic repression were identified and characterized in a single tumor population. Conclusion:The first evidence for combined HLA genetic and epigenetic defects in malignant cells was presented. Significance: Combinatorial immunotherapy harnessing T cell responses and DNA demethylation may counteract tumor immune resistance.

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Section: Discussionmentioning

confidence: 99%

“…LOH Analysis-The heterozygosity status of MHC was analyzed as reported (30) with primers listed in Table 1. LOH is defined as a LOH index (intensity of tumor allele one/intensity of tumor allele two)/(intensity of normal allele one/intensity of normal allele two) lower than 50%.…”

Section: Methodsmentioning

confidence: 99%

Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy

Chang

Pirozzi²,

Wen

et al. 2015

Journal of Biological Chemistry

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“…Both of them (forward primers) were tagged with a blue fluorescent label (FAM) and combined in the same tube, using 1-4 pmol of each primer (forward and reverse) because of their different size range. PCR, electrophoresis, and data analyses were done as described previously by Ramal et al [16]. Loss of heterozygosity (LOH) was recorded when the signal of one allele was reduced by Ͼ 25% in the tumor sample compared with the control stroma sample.…”

Section: Loss Of Heterozygosity Analysismentioning

confidence: 99%

High frequency of HLA-B44 allelic losses in human solid tumors

et al. 2003

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Human leukocyte antigen (HLA) class I downregulation, a frequent phenomenon observed in a variety of human tumors, favors tumor immune escape from T-lymphocyte recognition. However, it is not known whether a particular HLA class I allele is lost more frequently than others. To address this question we analyzed HLA class I expression in tumor tissues derived from 300 patients diagnosed as having breast, colorectal, or laryngeal carcinomas. Cryostatic tumor sections and a broad panel of anti-HLA class I monoclonal antibodies were used. We found that the HLA-B44 allele was lost more frequently than other HLA class I alleles, and that the difference was not related with changes in HLA-B44 allele frequencies between patients and controls. In addition, we observed that 35% of the HLA-B44 negative tumors presented HLA haplotype loss associated with loss of heterozygosity. These tests were performed on DNA samples obtained from microdissected tumor tissues. The results seem to indicate that HLA class I allelic losses are not randomly distributed during tumor development but that some HLA class I alleles, and HLA-B44 in particular, are more frequently downregulated and may play an important role in immune escape mechanisms. Human Immunology 64, 941-950 (2003).

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“…PCR products were detected on an ABI Prism 310 genetic analyzer (Applied Biosystems, Foster City, CA), using ROX500 as standard marker. Data were analyzed using GeneScan Analysis and Genotyper software and interpreted as described by Ramal et al 26 Briefly, LOH was assigned when more than 25% signal reduction of one allele was observed in the tumor sample as compared with the control peripheral blood lymphocytes sample.…”

Section: Loss Of Heterozygositymentioning

confidence: 99%

Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

Koning

Bovenschen

Leusink

et al. 2009

Intl Journal of Cancer

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Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes such as loss of heterozygosity (LOH) on human chromosome 18q21. This chromosomal region maps a gene cluster coding for a family of intracellular serine protease inhibitors (serpins), including SER-PINB13. As SERPINB13 expression in HNSCC has recently been shown to be downregulated both at the mRNA and protein levels, here we investigated if such a low SERPINB13 expression is associated with histopathological and clinical parameters of HNSCC tumors and patient survival. By generating specific antibodies followed by immunohistochemistry on a well-defined cohort of 99 HNSCC of the oral cavity and oropharynx, SERPINB13 expression was found to be partially or totally downregulated in 75% of the HNSCC as compared with endogenous expression in non-neoplastic epithelial cells. Downregulation of SERPINB13 protein expression in HNSCC was significantly associated with the presence of LOH at the SERPINB13 gene in the tumors (p 5 0.006), a poor differentiation grade of the tumors (p 5 0.001), the presence of a lymph node metastasis (p 5 0.012), and a decreased diseasefree (p 5 0.033) as well as overall (p 5 0.018) survival of the patients. This is the first report demonstrating that downregulation of SERPINB13 protein expression in HNSCC is positively associated with poor clinical outcome. Therefore, SERPINB13 seems to act as an important protease inhibitor involved in the progression of HNSCC. ' 2009 UICC

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Criteria to define HLA haplotype loss in human solid tumors

Cited by 40 publications

References 0 publications

Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy

Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy

High frequency of HLA-B44 allelic losses in human solid tumors

Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

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