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Matullo G.,University of Turin | Matullo G.,Genomic Variation in Human Population and Complex Diseases Unit | Gaetano C.D.,University of Turin | Gaetano C.D.,Genomic Variation in Human Population and Complex Diseases Unit | Guarrera S.,Genomic Variation in Human Population and Complex Diseases Unit
Environmental and Molecular Mutagenesis | Year: 2013

The allelic frequency spectrum emerging from several Next Generation Sequencing (NGS) projects is revealing important details about evolutionary and demographic forces that shaped the human genome. Herein, we discuss some of the achievements of the use of low-frequency and rare variants from NGS studies. The majority of variants that affect protein-coding regions are recent and rare. Often, the novel rare variants are enriched for deleterious alleles and are population-specific, making them suitable for the study of disease susceptibility. To investigate this kind of variation and its effects in association studies, very large sample sizes will be necessary to achieve sufficient statistical power. Moreover, as these variants are typically population-specific, the replication of disease associations across populations could be very difficult due to population stratification. Therefore, the design of experiments focusing on the identification of rare variants and their effects should be carefully planned. Although several successes have already been achieved through NGS for genetic epidemiology, pharmacogenetic and clinical purposes, with improvements of the sequencing technology and decreased costs, further advances are expected in the near future. Environ. Mol. Mutagen. 54:518-532, 2013. © 2013 Wiley Periodicals, Inc.


Matullo G.,Genomic Variation in Human Population and Complex Diseases Unit | Matullo G.,University of Turin | Naccarati A.,Molecular and Genetic Epidemiology Unit | Pardini B.,Genomic Variation in Human Population and Complex Diseases Unit | Pardini B.,University of Turin
International Journal of Cancer | Year: 2016

Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next-generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT-PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT-PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet-lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers. © 2015 UICC.


Matullo G.,Genomic Variation in Human Population and Complex Diseases Unit | Naccarati A.,Molecular and Genetic Epidemiology Unit | Pardini B.,Genomic Variation in Human Population and Complex Diseases Unit
International Journal of Cancer | Year: 2015

Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next-generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT-PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT-PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet-lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers. © 2015 UICC.


Tunesi S.,University of Piemonte Orientale | Tunesi S.,City of Health and Science Hospital | Ferrante D.,University of Piemonte Orientale | Mirabelli D.,City of Health and Science Hospital | And 17 more authors.
Carcinogenesis | Year: 2015

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor. © The Author 2015. Published by Oxford University Press. All rights reserved.


PubMed | Molecular and Genetic Epidemiology Unit and Genomic Variation in Human Population and Complex Diseases Unit
Type: Journal Article | Journal: International journal of cancer | Year: 2016

Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next-generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT-PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT-PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet-lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers.

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