Overexpression of G protein‐coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma

Atamaniuk, Johanna; Gleiß, Andreas; Porpaczy, Edit; Kainz, Birgit; Grunt, Thomas W.; Raderer, Markus; Hilgarth, Bernadette; Drach, Johannes; Ludwig, Heinz; Gisslinger, Heinz; Jaeger, Ulrich; Gaiger, Alexander

doi:10.1111/j.1365-2362.2012.02679.x

Cited by 103 publications

(80 citation statements)

References 26 publications

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“…19,20 GPRC5D and ITGA8 have not been described as plasma cells cell markers. However, elevated GPRC5D transcript levels have been associated with poor-prognosis MM, 21 and the ITGA8 transcript level decreases in MM cells treated with lenalidomide and pomalidomide.…”

Section: Resultsmentioning

confidence: 99%

Robust isolation of malignant plasma cells in multiple myeloma

Frigyesi

Adolfsson

Ali

et al. 2014

Blood

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• Molecular characterization of myeloma requires isolation of malignant plasma cells, which is currently hampered by the instability of CD138.• We identified CD319 and CD269 as robust replacements for CD138, facilitating molecular diagnostics in myeloma.Molecular characterization of malignant plasma cells is increasingly important for diagnostic and therapeutic stratification in multiple myeloma. However, the malignant plasma cells represent a relatively small subset of bone marrow cells, and need to be enriched prior to analysis. Currently, the cell surface marker CD138 (SDC1) is used for this enrichment, but has an important limitation in that its expression decreases rapidly after sampling. Seeking alternatives to CD138, we performed a computational screen for myeloma plasma cell markers and systematically evaluated 7 candidates. Our results conclusively show that the markers CD319 (SLAMF7/CS1) and CD269 (TNFRSF17/BCMA) are considerably more robust than CD138 and enable isolation of myeloma plasma cells under more diverse conditions, including the samples that have been delayed or frozen.Our results form the basis of improved procedures for characterizing cases of multiple myeloma in clinical practice. (Blood. 2014;123(9):1336-1340 IntroductionMultiple myeloma (MM) is characterized by the uncontrolled, clonal growth of plasma cells in the bone marrow. As our knowledge increases about the genetic basis of MM, and new therapeutic options are being developed, molecular characterization of MM plasma cells (MMPCs) is becoming increasingly important for subclassification, prognostication, and treatment stratification.

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Section: Resultsmentioning

confidence: 99%

Robust isolation of malignant plasma cells in multiple myeloma

Frigyesi

Adolfsson

Ali

et al. 2014

Blood

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“…Mutation of p53 causes derepression of GPRC5A, and proliferation, but paradoxically GPRC5A knockout mice experience high rates of adenoma and adenocarcinoma, as well as lung inflammation 65 . Expression of the nearby GPRC5D gene is reportedly localized to hard keratin tissues 66 , but more recently, expression in multiple myeloma has been suggested to be a highly specific tumor marker 67,68 . The SNP rs7308443 gave the best signal close to GPRC5D (nevus meta-analysis P = 0.009, melanoma meta-analysis P = 7.8e-5).…”

Section: Gprc5amentioning

confidence: 99%

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Duffy

Zhu

et al. 2017

Preprint

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The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, United Kingdom, and United States, comprising a total of 52,506 phenotyped individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs at a genome-wide level of significance in KITLG, DOCK8, and a broad region of 9q32. In a bivariate analysis combining the nevus results with those from a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level of significance. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis via genes we can show to be expressed under control of the MITF melanocytic cell lineage regulator.

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“…Besides, previous studies have suggested that GPRC5D could refer to the progression of many cancers [Cohen et al, ; Wolf et al, ]. Atamaniuk et al [] demonstrated that the overexpression of GPRC5D in the bone marrow was associated with poor prognosis of multiple myeloma. An integrated linkage analysis on a mouse model developed by Quigley et al [] reported that GPRC5D operated as a function node in the progression network of squamous cell carcinomas, which showed that GPRC5D gene could be a candidate cancer‐related gene in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Association between genetic variants in the promoter region of a novel antisense long noncoding RNA RP11‐392P7.6 and colorectal cancer risk

Jin

Ding

et al. 2017

Environ and Mol Mutagen

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There is a widespread occurrence of antisense transcripts' regulation on cancer-related genes in cancer biology. RP11-392P7.6 is antisense to the coding region of cancer-related gene GPRC5D, which has been found recently. The aim of this study was to investigate the associations of tagSNPs in the promoter region of RP11-392P7.6 with the risk of colorectal cancer. We conducted a two-stage case-control study, with a discovery set (320 cases and 319 controls) and a validation set (501 cases and 538 controls). Four tagSNPs (rs1531970, rs1642199, rs4763903, and rs10845671) were selected based on 1000 Genomes Project data and genotyped by using the Sequenom MassARRAY genotyping platform. In the discovery set, three tagSNPs (rs1642199, rs4763903, and rs10845671) were revealed promising associations with the risk of colorectal cancer, among which the rs10845671 variants were further replicated in the validation set (OR = 1.47, 95% CI = 1.10-1.20 in heterozygote codominant model; OR = 1.38, 95% CI = 1.04-1.83 in dominant model). When combined the two sets, the above positive associations remained unchanged. Rs10845671 was found to be associated with an increased risk of colorectal cancer (OR = 1.43, 95% CI = 1.14-1.81 in heterozygote codominant model; OR = 1.35, 95% CI = 1.08-1.69 in dominant model). These findings indicate that rs10845671 may contribute to the susceptibility to colorectal cancer and be a candidate biomarker for colorectal cancer risk prediction. Environ. Mol. Mutagen. 58:434-442, 2017. © 2017 Wiley Periodicals, Inc.

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Overexpression of G protein‐coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma

Abstract: Overexpression in poor-risk myeloma, low expression in normal tissues and cell surface expression identify GPRC5D as a potential novel cancer antigen. Our data demonstrate that GPRC5D is a prognostic factor in MM correlating with other major risk factors.

Cited by 103 publications

References 26 publications

Robust isolation of malignant plasma cells in multiple myeloma

Robust isolation of malignant plasma cells in multiple myeloma

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Association between genetic variants in the promoter region of a novel antisense long noncoding RNA RP11‐392P7.6 and colorectal cancer risk

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