Ivana Persico

@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{pmid37232846,

title = {PD-L1 Expression in Cutaneous Angiosarcomas: A Systematic Review with Meta-Analysis},

author = {Renato Lobrano and Panagiotis Paliogiannis and Angelo Zinellu and Giuseppe Palmieri and Ivana Persico and Arduino A Mangoni and Antonio Cossu},

doi = {10.3390/curroncol30050388},

issn = {1718-7729},

year  = {2023},

date = {2023-05-17},

urldate = {2023-05-17},

journal = {Curr Oncol},

volume = {30},

number = {5},

pages = {5135--5144},

abstract = {Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: "PD-L1" and "angiosarcomas". A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36-71%), with high heterogeneity (I = 84.81%,  < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly ( = 0.049) lower in Asian studies (ES = 35%, 95% CI 28-42%, I = 0.0%,  = 0.46) than in European studies (ES = 71%, 95% CI 51-89%, I = 48.91%,  = 0.12).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31497877,

title = {Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts},

author = {Buers, I. and Persico, I. and Schöning, L. and Nitschke, Y. and Di Rocco, M. and Loi, A. and Sahi, P. K. and Utine, G. E. and Bayraktar-Tanyeri, B. and Zampino, G. and Crisponi, G. and Rutsch, F. and Crisponi, L.},

year  = {2020},

date = {2020-01-01},

journal = {Clin Genet},

volume = {97},

number = {1},

pages = {209--221},

abstract = {Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of "CNTFR-related disorders" showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS-like phenotype. Therefore, retinitis pigmentosa and Bohring-Optiz syndrome-like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat-Hall/Schaaf-Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy-11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Angius2019,

title = {Confirmation of a new phenotype in an individual with a variant in the last part of exon 30 of CREBBP},

author = {Angius, A. and Uva, P. and Oppo, M. and Persico, I. and Onano, S. and Olla, S. and Pes, V. and Perria, C. and Cuccuru, G. and Atzeni, R. and Serra, G. and Cucca, F. and Sotgiu, S. and Hennekam, R. C. and Crisponi, L. },

year  = {2019},

date = {2019-01-01},

volume = {179},

number = {4},

pages = {634--638},

abstract = {We report here a novel de novo missense variant affecting the last amino acid of exon 30 of CREBBP [NM_004380, c.5170G>A; p.(Glu1724Lys)] in a 17-year-old boy presenting mild intellectual disability and dysmorphisms but not resembling the phenotype of classical Rubinstein-Taybi syndrome. The patient showed a marked overweight from early infancy on and had cortical heterotopias. Recently, 22 individuals have been reported with missense mutations in the last part of exon 30 and the beginning of exon 31 of CREBBP, showing this new phenotype. This additional case further delineates the genotype-phenotype correlations within the molecular and phenotypic spectrum of variants in CREBBP and EP300.},

note = {[DOI:hrefhttps://dx.doi.org/10.1002/ajmg.a.6105210.1002/ajmg.a.61052] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3073788730737887]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30859550,

title = {Exome sequencing in Crisponi/cold-induced sweating syndrome-like individuals reveals unpredicted alternative diagnoses},

author = {Angius, A. and Uva, P. and Oppo, M. and Buers, I. and Persico, I. and Onano, S. and Cuccuru, G. and Van Allen, M. I. and Hulait, G. and Aubertin, G. and Muntoni, F. and Fry, A. E. and Anner?n, G. and Stattin, E. L. and Palomares-Bralo, M. and Santos-Simarro, F. and Cucca, F. and Crisponi, G. and Rutsch, F. and Crisponi, L. },

year  = {2019},

date = {2019-01-01},

journal = {Clin Genet},

volume = {95},

number = {5},

pages = {607--614},

abstract = {Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by a complex phenotype (hyperthermia and feeding difficulties in the neonatal period, followed by scoliosis and paradoxical sweating induced by cold since early childhood) and a high neonatal lethality. CS/CISS is a genetically heterogeneous disorder caused by mutations in CRLF1 (CS/CISS1), CLCF1 (CS/CISS2) and KLHL7 (CS/CISS-like). Here, a whole exome sequencing approach in individuals with CS/CISS-like phenotype with unknown molecular defect revealed unpredicted alternative diagnoses. This approach identified putative pathogenic variations in NALCN, MAGEL2 and SCN2A. They were already found implicated in the pathogenesis of other syndromes, respectively the congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome, the Schaaf-Yang syndrome, and the early infantile epileptic encephalopathy-11 syndrome. These results suggest a high neonatal phenotypic overlap among these disorders and will be very helpful for clinicians. Genetic analysis of these genes should be considered for those cases with a suspected CS/CISS during neonatal period who were tested as mutation negative in the known CS/CISS genes, because an expedited and corrected diagnosis can improve patient management and can provide a specific clinical follow-up.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{angius_bi-allelic_2016,

title = {Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa},

author = {Andrea Angius and Paolo Uva and Insa Buers and Manuela Oppo and Alessandro Puddu and Stefano Onano and Ivana Persico and Angela Loi and Loredana Marcia and Wolfgang H{ö}hne and Gianmauro Cuccuru and Giorgio Fotia and Manila Deiana and Mara Marongiu and Hatice Tuba Atalay and Sibel Inan and Osama {El Assy} and Leo M E Smit and Ilyas Okur and Koray Boduroglu and G{ü}len Eda Utine and Esra Kılı{ç} and Giuseppe Zampino and Giangiorgio Crisponi and Laura Crisponi and Frank Rutsch},

doi = {10.1016/j.ajhg.2016.05.026},

issn = {1537-6605},

year  = {2016},

date = {2016-07-01},

journal = {American Journal of Human Genetics},

volume = {99},

number = {1},

pages = {236--245},

abstract = {Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1) is a very rare autosomal-recessive disorder characterized by a complex phenotype with high neonatal lethality, associated with the following main clinical features: hyperthermia and feeding difficulties in the neonatal period, scoliosis, and paradoxical sweating induced by cold since early childhood. CS/CISS1 can be caused by mutations in cytokine receptor-like factor 1 (CRLF1). However, the physiopathological role of CRLF1 is still poorly understood. A subset of CS/CISS1 cases remain yet genetically unexplained after CRLF1 sequencing. In five of them, exome sequencing and targeted Sanger sequencing identified four homozygous disease-causing mutations in kelch-like family member 7 (KLHL7), affecting the Kelch domains of the protein. KLHL7 encodes a BTB-Kelch-related protein involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mono-allelic substitutions in other domains of KLHL7 have been reported in three families affected by a late-onset form of autosomal-dominant retinitis pigmentosa. Retinitis pigmentosa was also present in two surviving children reported here carrying bi-allelic KLHL7 mutations. KLHL7 mutations are thus associated with a more severe phenotype in recessive than in dominant cases. Although these data further support the pathogenic role of KLHL7 mutations in a CS/CISS1-like phenotype, they do not explain all their clinical manifestations and highlight the high phenotypic heterogeneity associated with mutations in KLHL7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kottgen_genome-wide_2013,

title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations},

author = {K{ö}ttgen, Anna and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and ... and Tore, Silvia and ... and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Chasman, Daniel I and Raitakari, Olli and Kao, W H Linda and Ciullo, Marina and Fox, Caroline S and Caulfield, Mark and Bochud, Murielle and Gieger, Christian},

doi = {10.1038/ng.2500},

issn = {1546-1718},

year  = {2013},

date = {2013-02-01},

urldate = {2013-02-01},

journal = {Nature Genetics},

volume = {45},

number = {2},

pages = {145--154},

abstract = {Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}