ORCID Profile
0000-0001-6538-9705
Current Organisations
National Cancer Institute
,
Hue University
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Publisher: Springer Science and Business Media LLC
Date: 20-01-2021
Publisher: Informa UK Limited
Date: 15-04-2016
Publisher: American Association for Cancer Research (AACR)
Date: 09-2015
DOI: 10.1158/2159-8290.CD-15-0125
Abstract: Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10−9 OR, 2.43 95% confidence interval, 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene. Significance: Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma. Cancer Discov 5(9) 920–31. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 893
Publisher: Informa UK Limited
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 09-06-2017
DOI: 10.1038/NCOMMS15724
Abstract: Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P =3.1 × 10 −10 ), 3p22.1 (rs67311347, P =2.5 × 10 −8 ), 3q26.2 (rs10936602, P =8.8 × 10 −9 ), 8p21.3 (rs2241261, P =5.8 × 10 −9 ), 10q24.33-q25.1 (rs11813268, P =3.9 × 10 −8 ), 11q22.3 (rs74911261, P =2.1 × 10 −10 ) and 14q24.2 (rs4903064, P =2.2 × 10 −24 ). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2014
DOI: 10.1038/NG.3094
Publisher: Oxford University Press (OUP)
Date: 09-02-2016
DOI: 10.1093/HMG/DDW027
Publisher: Springer Science and Business Media LLC
Date: 08-06-2022
DOI: 10.1038/S41586-022-04809-8
Abstract: Large-scale human genetic data 1–3 have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient s les, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor ( VHL ) 4–6 . VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2α (HIF2A) stabilization 6,7 . We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 ( CCND1 ) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele C at rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated licons at 8q21.3-q24.3 (ref. 8 ). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2022
DOI: 10.1158/1055-9965.EPI-22-0043
Abstract: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P & 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37 95% confidence interval (CI) = 1.09–1.73 P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19 95% CI = 1.01–1.41 P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.
Publisher: Informa UK Limited
Date: 19-02-2022
Publisher: Public Library of Science (PLoS)
Date: 03-01-2019
Publisher: Elsevier BV
Date: 12-2021
Publisher: Springer Science and Business Media LLC
Date: 2021
No related grants have been discovered for Mitchell Machiela.