| 1. |
- Litchfield, K, et al.
(author)
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Identification of four new susceptibility loci for testicular germ cell tumour
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8690-
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we conducted a multistage GWAS with a combined data set of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P=1.5 × 10−9), 11q14.1 (rs7107174, GAB2, P=9.7 × 10−11), 16p13.13 (rs4561483, GSPT1, P=1.6 × 10−8) and 16q24.2 (rs55637647, ZFPM1, P=3.4 × 10−9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.
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| 2. |
- Nsengimana, Jérémie, et al.
(author)
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Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:13, s. 11683-11693
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Journal article (peer-reviewed)abstract
- Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.
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