Alessandro Testori
Assegnista di ricerca (Research grant)
Area of interest:
My research mainly focuses on the investigation of genetic susceptibility in complex traits through genome-wide association studies and computational approaches.
I am currently working to unravel the genetic basis underlying interindividual variability to COVID-19 infection, which is one of the aims of the SerGenCOVID-19 (Serum Genetic COVID-19) project.
Most significant publications:
2023
Formicola, D.; Lasorsa, V. A.; Cantalupo, S.; Testori, A.; Cardinale, A.; Avitabile, M.; Diskin, S.; Iolascon, A.; Capasso, M.
CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity Journal Article
In: HGG Adv, 4 (1), pp. 100158, 2023.
@article{pmid36425957,
title = {CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity},
author = {D. Formicola and V. A. Lasorsa and S. Cantalupo and A. Testori and A. Cardinale and M. Avitabile and S. Diskin and A. Iolascon and M. Capasso},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {HGG Adv},
volume = {4},
number = {1},
pages = {100158},
abstract = {acts as oncogene in NB. In addition, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.},
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acts as oncogene in NB. In addition, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.
2022
Testori, A.; Vaksman, Z.; Diskin, S. J.; Hakonarson, H.; Capasso, M.; Iolascon, A.; Maris, J. M.; Devoto, M.
Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility Journal Article
In: Cancer Epidemiol Biomarkers Prev, 31 (4), pp. 870–875, 2022.
@article{pmid35131881,
title = {Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility},
author = {A. Testori and Z. Vaksman and S. J. Diskin and H. Hakonarson and M. Capasso and A. Iolascon and J. M. Maris and M. Devoto},
year = {2022},
date = {2022-04-01},
journal = {Cancer Epidemiol Biomarkers Prev},
volume = {31},
number = {4},
pages = {870--875},
abstract = {Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease. We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs. 10-6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs. These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion. This work supports the need for GWAS to be performed in populations of all races and ethnicities.},
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pubstate = {published},
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Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease. We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs. 10-6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs. These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion. This work supports the need for GWAS to be performed in populations of all races and ethnicities.
Cardinale, A.; Cantalupo, S.; Lasorsa, V. A.; Montella, A.; Cimmino, F.; Succoio, M.; Vermeulen, M.; Baltissen, M. P.; Esposito, M.; Avitabile, M.; Formicola, D.; Testori, A.; Bonfiglio, F.; Ghiorzo, P.; Scalvenzi, M.; Ayala, F.; Zambrano, N.; Iles, M. M.; Xu, M.; Law, M. H.; Brown, K. M.; Iolascon, A.; Capasso, M.
Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1 Journal Article
In: Hum Mol Genet, 31 (6), pp. 863–874, 2022.
@article{pmid34605909,
title = {Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1},
author = {A. Cardinale and S. Cantalupo and V. A. Lasorsa and A. Montella and F. Cimmino and M. Succoio and M. Vermeulen and M. P. Baltissen and M. Esposito and M. Avitabile and D. Formicola and A. Testori and F. Bonfiglio and P. Ghiorzo and M. Scalvenzi and F. Ayala and N. Zambrano and M. M. Iles and M. Xu and M. H. Law and K. M. Brown and A. Iolascon and M. Capasso},
year = {2022},
date = {2022-03-01},
journal = {Hum Mol Genet},
volume = {31},
number = {6},
pages = {863--874},
abstract = {The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.33 using epigenomic annotations and in vitro reporter gene assays to identify regulatory variants. We found two putative functional single nucleotide polymorphisms (SNPs) in an enhancer and in the promoter of OBFC1, respectively, in neural crest and CMM cells, one, rs2995264, altering enhancer activity. The minor allele G of rs2995264 correlated with lower OBFC1 expression in 470 CMM tumors and was confirmed to increase the CMM risk in a cohort of 484 CMM cases and 1801 controls of Italian origin. Hi-C and chromosome conformation capture (3C) experiments showed the interaction between the enhancer-SNP region and the promoter of OBFC1 and an isogenic model characterized by CRISPR-Cas9 deletion of the enhancer-SNP region confirmed the potential regulatory effect of rs2995264 on OBFC1 transcription. Moreover, the presence of G-rs2995264 risk allele reduced the binding affinity of the transcription factor MEOX2. Biologic investigations showed significant cell viability upon depletion of OBFC1, specifically in CMM cells that were homozygous for the protective allele. Clinically, high levels of OBFC1 expression associated with histologically favorable CMM tumors. Finally, preliminary results suggested the potential effect of decreased OBFC1 expression on telomerase activity in tumorigenic conditions. Our results support the hypothesis that reduced expression of OBFC1 gene through functional heritable DNA variation can contribute to malignant transformation of normal melanocytes.},
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The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.33 using epigenomic annotations and in vitro reporter gene assays to identify regulatory variants. We found two putative functional single nucleotide polymorphisms (SNPs) in an enhancer and in the promoter of OBFC1, respectively, in neural crest and CMM cells, one, rs2995264, altering enhancer activity. The minor allele G of rs2995264 correlated with lower OBFC1 expression in 470 CMM tumors and was confirmed to increase the CMM risk in a cohort of 484 CMM cases and 1801 controls of Italian origin. Hi-C and chromosome conformation capture (3C) experiments showed the interaction between the enhancer-SNP region and the promoter of OBFC1 and an isogenic model characterized by CRISPR-Cas9 deletion of the enhancer-SNP region confirmed the potential regulatory effect of rs2995264 on OBFC1 transcription. Moreover, the presence of G-rs2995264 risk allele reduced the binding affinity of the transcription factor MEOX2. Biologic investigations showed significant cell viability upon depletion of OBFC1, specifically in CMM cells that were homozygous for the protective allele. Clinically, high levels of OBFC1 expression associated with histologically favorable CMM tumors. Finally, preliminary results suggested the potential effect of decreased OBFC1 expression on telomerase activity in tumorigenic conditions. Our results support the hypothesis that reduced expression of OBFC1 gene through functional heritable DNA variation can contribute to malignant transformation of normal melanocytes.
2020
Ävitabile, M.; Succoio, M.; Testori, A.; Cardinale, A.; Vaksman, Z.; Lasorsa, V. A.; Cantalupo, S.; Esposito, M.; Cimmino, F.; Montella, A.; Formicola, D.; Koster, J.; Andreotti, V.; Ghiorzo, P.; Romano, M. F.; Staibano, S.; Scalvenzi, M.; Ayala, F.; Hakonarson, H.; Corrias, M. V.; Devoto, M.; Law, M. H.; Iles, M. M.; Brown, K.; Diskin, S.; Zambrano, N.; Iolascon, A.; Capasso, M.
Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene Journal Article
In: Carcinogenesis, 41 (3), pp. 284–295, 2020.
@article{pmid31605138,
title = {Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene},
author = {M. Ävitabile and M. Succoio and A. Testori and A. Cardinale and Z. Vaksman and V. A. Lasorsa and S. Cantalupo and M. Esposito and F. Cimmino and A. Montella and D. Formicola and J. Koster and V. Andreotti and P. Ghiorzo and M. F. Romano and S. Staibano and M. Scalvenzi and F. Ayala and H. Hakonarson and M. V. Corrias and M. Devoto and M. H. Law and M. M. Iles and K. Brown and S. Diskin and N. Zambrano and A. Iolascon and M. Capasso},
year = {2020},
date = {2020-05-01},
urldate = {2020-05-01},
journal = {Carcinogenesis},
volume = {41},
number = {3},
pages = {284--295},
abstract = {10-4 demonstrated enrichment of biological processes such as cell migration, cell cycle, metabolism and immune response, which are essential of human NCC development, underlying both tumors. In vitro and in silico analyses indicated that the rs2153977-T protective allele, located in an NB and CMM enhancer, decreased expression of SLC16A1 via long-range loop formation and altered a T-box protein binding site. Upon depletion of SLC16A1, we observed a decrease of cellular proliferation and invasion in both NB and CMM cell lines, suggesting its role as oncogene. This is the largest study to date examining pleiotropy across two NC cell-derived tumors identifying 1p13.2 as common susceptibility locus for NB and CMM risk. We demonstrate that combining genome-wide association studies results across cancers with same origins can identify new loci common to neuroblastoma and melanoma arising from tissues which originate from neural crest cells. Our results also show 1p13.2 confer risk to neuroblastoma and melanoma by regulating SLC16A1.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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10-4 demonstrated enrichment of biological processes such as cell migration, cell cycle, metabolism and immune response, which are essential of human NCC development, underlying both tumors. In vitro and in silico analyses indicated that the rs2153977-T protective allele, located in an NB and CMM enhancer, decreased expression of SLC16A1 via long-range loop formation and altered a T-box protein binding site. Upon depletion of SLC16A1, we observed a decrease of cellular proliferation and invasion in both NB and CMM cell lines, suggesting its role as oncogene. This is the largest study to date examining pleiotropy across two NC cell-derived tumors identifying 1p13.2 as common susceptibility locus for NB and CMM risk. We demonstrate that combining genome-wide association studies results across cancers with same origins can identify new loci common to neuroblastoma and melanoma arising from tissues which originate from neural crest cells. Our results also show 1p13.2 confer risk to neuroblastoma and melanoma by regulating SLC16A1.
2018
Cimmino, F.; Avitabile, M.; Diskin, S. J.; Vaksman, Z.; Pignataro, P.; Formicola, D.; Cardinale, A.; Testori, A.; Koster, J.; Torres, C.; Devoto, M.; Maris, J. M.; Iolascon, A.; Capasso, M.
Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARĐ1 as tumor-suppressor Journal Article
In: Int J Cancer, 143 (11), pp. 2828–2837, 2018.
@article{pmid30132831,
title = {Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARĐ1 as tumor-suppressor},
author = {F. Cimmino and M. Avitabile and S. J. Diskin and Z. Vaksman and P. Pignataro and D. Formicola and A. Cardinale and A. Testori and J. Koster and C. Torres and M. Devoto and J. M. Maris and A. Iolascon and M. Capasso},
year = {2018},
date = {2018-12-01},
journal = {Int J Cancer},
volume = {143},
number = {11},
pages = {2828--2837},
abstract = {, OR:0.65, 95% CI:0.58-0.73). Particularly, the T risk allele of rs17489363 in the canonical promoter region of full-length BARD1 altered binding site of the transcription factor HSF1 and correlated with low expression of full-length BARD1 mRNA and protein. Low-level expression of full-length BARD1 associated with advanced neuroblastoma. In human neuroblastoma cells, attenuating full-length BARD1 increased proliferation and invasion capacity. In conclusion, we have identified two potentially causative SNPs at the BARD1 locus associated with predisposition to high-risk neuroblastoma, and have shown that full-length BARD1 may act as tumor suppressor.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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, OR:0.65, 95% CI:0.58-0.73). Particularly, the T risk allele of rs17489363 in the canonical promoter region of full-length BARD1 altered binding site of the transcription factor HSF1 and correlated with low expression of full-length BARD1 mRNA and protein. Low-level expression of full-length BARD1 associated with advanced neuroblastoma. In human neuroblastoma cells, attenuating full-length BARD1 increased proliferation and invasion capacity. In conclusion, we have identified two potentially causative SNPs at the BARD1 locus associated with predisposition to high-risk neuroblastoma, and have shown that full-length BARD1 may act as tumor suppressor.
- Monserrato
alessandrotestori7@gmail.com
070 6754593
ORCID profile: http://orcid.org/0000-0001-6088-730X
