Maria Grazia Doro

@article{pmid38280995,

title = {Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population},

author = {Maria Cristina Sini and Maria Grazia Doro and Laura Frogheri and Angelo Zinellu and Panagiotis Paliogiannis and Alberto Porcu and Fabrizio Scognamillo and Daniele Delogu and Davide Adriano Santeufemia and Ivana Persico and Grazia Palomba and Giovanni Battista Maestrale and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12967-024-04923-3},

issn = {1479-5876},

year  = {2024},

date = {2024-01-27},

urldate = {2024-01-27},

journal = {J Transl Med},

volume = {22},

number = {1},

pages = {108},

abstract = {BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia.



METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms.



RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival.



CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doro_molecular_2017,

title = {Molecular Characterization of beta-Thalassemia Mutations in Central Vietnam.},

author = {Doro, Maria G. and Casu, Giuseppina and Frogheri, Laura and Persico, Ivana and Triet, Le Phan Minh and Hoa, Phan Thi Thuy and Hoang, Nguyen Huy and Pirastru, Monica and Mereu, Paolo and Cucca, Francesco and Masala, Bruno},

doi = {10.1080/03630269.2017.1321013},

issn = {1532-432X 0363-0269},

year  = {2017},

date = {2017-03-01},

journal = {Hemoglobin},

volume = {41},

number = {2},

pages = {96--99},

abstract = {The molecular basis of beta-thalassemia (beta-thal) mutations in North and in South Vietnam have been described during the past 15 years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of beta-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the beta(0) and two of the beta(+) type) in a total of 48 chromosomes. The most common was codon 26 (GtextgreaterA) or Hb E (HBB: c.79 GtextgreaterA) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (AtextgreaterT) (HBB: c.52 AtextgreaterT) (25.0%), and codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3-8.3%) were IVS-I-1 (GtextgreaterT) (HBB: c.92+1 GtextgreaterT), codon 26 (GtextgreaterT) (HBB: c.79 GtextgreaterT) and codons 71/72 (+A) (HBB: c.216_217insA). Relatively rarer (2.0%) were the promoter -28 (AtextgreaterG) (HBB: c.78 AtextgreaterG) mutation, the codon 95 (+A) (HBB: c.287_288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45_46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for beta-thal prevention and control in the region as well as in the whole country.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doro_phylogeny_2014,

title = {Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes},

author = {Maria Grazia Doro and Daniela Piras and Giovanni Giuseppe Leoni and Giuseppina Casu and Simona Vaccargiu and Debora Parracciani and Salvatore Naitana and Mario Pirastu and Andrea Novelletto},

doi = {10.1371/journal.pone.0095969},

issn = {1932-6203},

year  = {2014},

date = {2014-01-01},

journal = {PloS One},

volume = {9},

number = {4},

pages = {e95969},

abstract = {We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{piras_haplotype_2012,

title = {Haplotype affinities resolve a major component of goat (Capra hircus) MtDNA D-loop diversity and reveal specific features of the Sardinian stock},

author = {Daniela Piras and Maria Grazia Doro and Giuseppina Casu and Paola Maria Melis and Simona Vaccargiu and Ignazio Piras and Debora Parracciani and Roberta Stradoni and Bruno Frongia and Graziano Lai and Salvatore Sale and Walter Cattari and Roberto Piras and Ombretta Querci and Piergiorgio Demuro and Sandro Cui and Franco Atzori and Marco Mancosu and Francesca Marchiori and Rossana Cammelli and Alessandra Spiga and Pier Paolo Loddo and Gianfranco Pili and Roberto Boi and Giuseppe Argiolas and Paolo Mereu and Giovanni Giuseppe Leoni and Salvatore Naitana and Mario Pirastu and Andrea Novelletto},

doi = {10.1371/journal.pone.0030785},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PloS One},

volume = {7},

number = {2},

pages = {e30785},

abstract = {Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12826371,

title = {T-cell receptor repertoire in healthy Sardinian subjects},

author = {Bonfigli, S. and Doro, M. G. and Fozza, C. and Derudas, D. and Dore, F. and Longinotti, M.},

year  = {2003},

date = {2003-07-01},

journal = {Hum Immunol},

volume = {64},

number = {7},

pages = {689--695},

abstract = {The T-cell receptor (TCR) Vbeta gene usage of CD4+ and CD8+ T-cell subpopulations was evaluated by flow cytometric analysis and by CDR3 spectratyping in healthy subjects belonging to Sardinian population, which is ethnically homogeneous and genetically distant from all other Italian and Caucasoid groups. As described in healthy Caucasian subjects, we found a nonrandom Vbeta gene usage and in some Vbeta families a significant skewed reactivity toward CD4+ T cells. Moreover, different subjects showed expansions in some Vbeta subfamilies, mainly in the CD8+ T cells. By CDR3 spectratyping analysis we found a significantly higher degree of skewness in the TCR Vbeta repertoire of CD8+ than in that of CD4+ T cells. The similarity found in the TCR Vbeta gene usage between the population examined and other Caucasoid groups suggest that the shape of the TCR repertoire is more influenced by rearrangement processes than ethnic background. However, genetic polymorphisms may condition the expression levels of some Vbetas, determining the variability of the TCR repertoire between different populations. Finally, the profound perturbations evidenced in the CD8+ T cell subpopulation could be related to a different response to the antigenic stimulation between CD8+ and CD4+ T lymphocytes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}