المؤلفون: Ning Zhang, Luuk Harbers, Michele Simonetti, Constantin Diekmann, Quentin Verron, Enrico Berrino, Sara E. Bellomo, Gabriel M. C. Longo, Michael Ratz, Niklas Schultz, Firas Tarish, Peng Su, Bo Han, Wanzhong Wang, Sofia Onorato, Dora Grassini, Roberto Ballarino, Silvia Giordano, Qifeng Yang, Anna Sapino, Jonas Frisén, Kanar Alkass, Henrik Druid, Vassilis Roukos, Thomas Helleday, Caterina Marchiò, Magda Bienko, Nicola Crosetto

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: ‘pseudo-diploid’ cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/a7bc352b5e9d473f9b3b201fba7c47d9Test

المؤلفون: Natalia Malara, Maria Laura Coluccio, Fabiana Grillo, Teresa Ferrazzo, Nastassia C. Garo, Giuseppe Donato, Annamaria Lavecchia, Franco Fulciniti, Anna Sapino, Eliano Cascardi, Antonella Pellegrini, Prassede Foxi, Cesare Furlanello, Giovanni Negri, Guido Fadda, Arrigo Capitanio, Salvatore Pullano, Virginia M. Garo, Francesca Ferrazzo, Alarice Lowe, Angela Torsello, Patrizio Candeloro, Francesco Gentile

المصدر: Molecular Cancer, Vol 23, Iss 1, Pp 1-5 (2024)

مصطلحات موضوعية: Cancer prevention, Liquid biopsy, Multicancer diagnosis, Non heamatological proliferating cells, Predictive model, Supervised machine learning, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background the problem in early diagnosis of sporadic cancer is understanding the individual’s risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation. Methods a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction. Results the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity. Conclusion this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1476-4598Test

الوصول الحر: https://doaj.org/article/3afe383205ca4c4bb4fbd6e1c3d0d554Test

المؤلفون: Eros Azzalini, Barbara Di Stefano, Vincenzo Canzonieri, Tiziana Venesio, Umberto Miglio, Caterina Marchiò, Anna Sapino, Carlo Previderè, Paolo Fattorini, Serena Bonin

المصدر: Methods and Protocols, Vol 7, Iss 3, p 40 (2024)

مصطلحات موضوعية: nCounter, RNA, RNA degradation, FFPE, Bouin, RT-qPCR, Biology (General), QH301-705.5

الوصف: Archive tissues are the most available source of human tissues useful for molecular analysis in translational research. The main issues for those specimens are the modification and degradation of biomolecules, namely proteins, DNA, and RNA. In the last decade, several high-throughput analytical methods have been applied to archive tissues. Although histological tissues are fixed in neutral-buffered formalin nowadays, in the recent past, Bouin’s solution was also used in tissue processing. The present study aims to investigate the feasibility of nCounter Nanostring hybridization in quantifying mRNA in highly degraded samples, such as Bouin’s fixed and paraffin-embedded (BFPE) tissues, in comparison to the standard formalin-fixed and paraffin-embedded (FFPE) tissues as a source of RNA. A total of 16 paraffin-embedded tissue blocks from eight patients were analyzed (8 were FFPE and 8 were BEPE). Nanostring technology was applied to 300 ng of each RNA sample, whereas 360 ng of the same templates were retrotranscribed and submitted to qPCR and ddPCR. Our results show that the Nanostring technology outperforms the reference methods (ddPCR and qPCR) in detecting target mRNA in FFPE and BFPE samples. However, even Nanostring technology does not escape the limitation imposed by the degradation of the RNA templates, which could lead to misleading conclusions on the gene expression level.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2409-9279/7/3/40Test; https://doaj.org/toc/2409-9279Test

الوصول الحر: https://doaj.org/article/55e3a761e7fc4e8c9692838da1c65ec7Test

المؤلفون: Giancarlo Pruneri, Daniele Lorenzini, Mauro G. Mastropasqua, Giuseppe Perrone, Antonio Rizzo, Donatella Santini, Chiara C. Volpi, Saverio Cinieri, Alberto Zambelli, Anna Sapino, Isabella Castellano

المصدر: npj Breast Cancer, Vol 9, Iss 1, Pp 1-4 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Multigenic tests represent an essential tool for the selection of adjuvant therapy in estrogen-positive/HER2-negative (ER + /HER2-) early breast cancer (BC). The workflow of these tests, either if they are externalized or carried out in-house, generates a workload for the pathology laboratories, that is often underestimated and may affect timely therapy initiation. Here, we describe the evolving role of pathology laboratories in using multigenic tests and, more in general, in providing adequate tissue for molecular analyses. Moreover, we propose a “reflex testing” model, in which pathologists, based on pre-specified and shared criteria, are expected to action multigene testing independently of multidisciplinary team discussion in ER + /HER2- BC patients, in order to optimize turnaround time and proper therapy intervention.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2374-4677Test

الوصول الحر: https://doaj.org/article/69dd406149ad42729238c4c9f88b56fdTest

المؤلفون: Enrico Berrino, Laura Annaratone, Sara Erika Bellomo, Giulio Ferrero, Amedeo Gagliardi, Alberto Bragoni, Dora Grassini, Simonetta Guarrera, Caterina Parlato, Laura Casorzo, Mara Panero, Ivana Sarotto, Silvia Giordano, Matteo Cereda, Filippo Montemurro, Riccardo Ponzone, Nicola Crosetto, Alessio Naccarati, Anna Sapino, Caterina Marchiò

المصدر: Genome Medicine, Vol 14, Iss 1, Pp 1-16 (2022)

مصطلحات موضوعية: Breast cancer, HER2, HER2-low, Heterogeneity, Classification, Mutation, Medicine, Genetics, QH426-470

الوصف: Abstract Background The “HER2-low” nomenclature identifies breast carcinomas (BCs) displaying a HER2 score of 1+/2+ in immunohistochemistry and lacking ERBB2 amplification. Whether HER2-low BCs (HLBCs) constitute a distinct entity is debated. Methods We performed DNA and RNA high-throughput analysis on 99 HLBC samples (n = 34 cases with HER2 score 1+/HLBC-1, n = 15 cases with HER2 score 2+ and ERBB2 not amplified/HLBC-2N, and n = 50 cases with score 2+ and ERBB2 copy number in the equivocal range/HLBC-2E). We compared the mutation rates with data from 1317 samples in the Memorial Sloan-Kettering Cancer Center (MSKCC) BC cohort and gene expression data with those from an internal cohort of HER2-negative and HER2-positive BCs. Results The most represented mutations affected PIK3CA (31/99, 31%), GATA3 (18/99, 18%), TP53 (17/99, 17%), and ERBB2 (8/99, 8%, private to HLBC-2E). Tumor mutational burden was significantly higher in HLBC-1 compared to HLBC-2E/N (P = 0.04). Comparison of mutation spectra revealed that HLBCs were different from both HER2-negative and HER2-positive BCs, with HLBC-1 resembling more HER2-negative tumors and HLBC-2 mutationally related to HER2-addicted tumors. Potentially actionable alterations (annotated by using OncoKB/ESCAT classes) affected 52 patients. Intra-group gene expression revealed overlapping features between HLBC-1 and control HER2-negative BCs, whereas the HLBC-2E tumors showed the highest diversity overall. The RNA-based class discovery analysis unveiled four subsets of tumors with (i) lymphocyte activation, (ii) unique enrichment in HER2-related features, (iii) stromal remodeling alterations, and (iv) actionability of PIK3CA mutations (LAURA classification). Conclusions HLBCs harbor distinct genomic features when compared with HER2-positive and HER2-negative BCs; however, differences across IHC classes were also unveiled thus dissecting the full picture of heterogeneity across HER2-low disease. The HLBC-2E category harbors most distinctive features, whereas HLBC-1 seems superimposable to HER2-negative disease. Further studies are needed to ascertain whether the four genomic-driver classes of the LAURA classification hold prognostic and/or predictive implications.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-994XTest

الوصول الحر: https://doaj.org/article/bd792d56b3094029b4da87b8d57caeffTest

المؤلفون: Enrico Berrino, Roberto Filippi, Clara Visintin, Serena Peirone, Elisabetta Fenocchio, Giovanni Farinea, Franco Veglio, Massimo Aglietta, Anna Sapino, Matteo Cereda, Rosella Visintin, Barbara Pasini, Caterina Marchiò

المصدر: npj Precision Oncology, Vol 6, Iss 1, Pp 1-9 (2022)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract The onset of multiple and metachronous tumors in young patients induces to suspect the presence of genetic variants in genes associated with tumorigenesis. We describe here the unusual case of a 16-year-old patient who developed a synchronous bifocal colorectal adenocarcinoma with distant metastases. We provide high throughput molecular characterization with whole-exome sequencing (WES) and DNA targeted sequencing of different tumoral lesions and normal tissue samples that led to unveil a germline POLE mutation (p.Ser297Cys) coexisting with the PMS2 c.2174 + 1 G > A splicing mutation. This clinical scenario defines a “POLE-LYNCH” collision syndrome, which explains the ultra-mutator phenotype observed in the tumor lesions, and the presence of MMR deficiency-associated unusual signatures. The patient was successfully treated with immune checkpoint inhibitors but subsequently developed a high-grade urothelial carcinoma cured by surgery. We complement this analysis with a transcriptomic characterization of tumoral lesions with a panel targeting 770 genes related to the tumor microenvironment and immune evasion thus getting insight on cancer progression and response to immunotherapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2397-768XTest

الوصول الحر: https://doaj.org/article/0dc23024ce6348309ded7e0db960bd7fTest

المؤلفون: Carlos Sebastian, Christina Ferrer, Maria Serra, Jee-Eun Choi, Nadia Ducano, Alessia Mira, Manasvi S. Shah, Sylwia A. Stopka, Andrew J. Perciaccante, Claudio Isella, Daniel Moya-Rull, Marianela Vara-Messler, Silvia Giordano, Elena Maldi, Niyati Desai, Diane E. Capen, Enzo Medico, Murat Cetinbas, Ruslan I. Sadreyev, Dennis Brown, Miguel N. Rivera, Anna Sapino, David T. Breault, Nathalie Y. R. Agar, Raul Mostoslavsky

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022)

مصطلحات موضوعية: Science

الوصف: Metabolic reprogramming upon SIRT6 loss induces tumour formation in the intestine but the mechanism is unclear. Here, the authors show that loss of SIRT6 leads to the expansion of epithelial cells with high pyruvate dehydrogenase kinase activity resulting in enhanced stem cell activity and tumour-initiating potential

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/1ae650e5a5c942e78cc7775f36dd9685Test

المؤلفون: Fabio Conforti, Laura Pala, Eleonora Pagan, Elena Guerini Rocco, Vincenzo Bagnardi, Emilia Montagna, Giulia Peruzzotti, Tommaso De Pas, Caterina Fumagalli, Silvana Pileggi, Chiara Pesenti, Sergio Marchini, Giovanni Corso, Caterina Marchio’, Anna Sapino, Rossella Graffeo, Laetitia Collet, Philippe Aftimos, Christos Sotiriou, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Marco Colleoni, Aron Goldhirsch

المصدر: Breast, Vol 59, Iss , Pp 94-101 (2021)

مصطلحات موضوعية: Triple negative invasive lobular carcinoma, ERBB2 gene mutations, HER2/PI3K/AKT pathway, Androgen receptor, Luminal androgen receptor subtype, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs) Methods: We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012.Primary objective was to assess the invasive disease-free survival(iDFS).Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2-gene.Additionally, DNA mutational status of an independent cohort of 45 TN-ILCs from three databases were analyzed, to confirm mutations in ERBB2-gene and to identify other recurrently mutated genes. Results: Among 4152 ILCs, 74(1.8%) were TN and were analyzed.The iDFS at 5 and 10 years of FUP were 50.4%(95%CI,38.0–61.6) and 37.2%(95%CI,25.5–48.8), respectively.The molecular subtype was defined through PAM50-classifier for 31 out of 74 TN-ILCs: 48% were Luminal-A(15/31), 3% luminal-B(1/31), 32% HER2-enriched (10/31), and only 16% basal-like(5/31).Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 94% of luminal tumors versus 53% in non-luminal tumors; p-value = 0.001).20% of TN-ILCs analyzed(7/35), harbored a pathogenetic and actionable mutation in the ERBB2-gene. Analysis of the independent cohort of 45 TN-ILCs from three different databases, confirmed similar percentage of pathogenetic and actionable mutations in ERBB2-gene(20%; 9/45).Among the top 10 molecular pathways significantly enriched for recurrently mutated genes in TN-ILCs(FDR

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S0960977621004070Test; https://doaj.org/toc/1532-3080Test

الوصول الحر: https://doaj.org/article/0e41cdfb84f743128a8f6f2c40685bb2Test

المؤلفون: Michele Simonetti, Ning Zhang, Luuk Harbers, Maria Grazia Milia, Silvia Brossa, Thi Thu Huong Nguyen, Francesco Cerutti, Enrico Berrino, Anna Sapino, Magda Bienko, Antonino Sottile, Valeria Ghisetti, Nicola Crosetto

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021)

مصطلحات موضوعية: Science

الوصف: Genomic surveillance of SARS-CoV-2 is crucial to monitor the spread of variants of concern. A new sequencing method enables cost-effective SARS-CoV-2 genomic surveillance at scale and is easily adaptable to other viruses.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/59ac650297524e1a915ee584a53ec570Test

المؤلفون: Federica Verginelli, Alberto Pisacane, Gennaro Gambardella, Antonio D’Ambrosio, Ermes Candiello, Marco Ferrio, Mara Panero, Laura Casorzo, Silvia Benvenuti, Eliano Cascardi, Rebecca Senetta, Elena Geuna, Andrea Ballabio, Filippo Montemurro, Anna Sapino, Paolo M. Comoglio, Carla Boccaccio

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)

مصطلحات موضوعية: Science

الوصف: Cancer of unknown primary (CUP) is a mysterious malignancy featuring metastatic dissemination in the absence of a recognizable primary tumor. By characterizing CUP cancer stem cells we show that self-sustained long-term propagation and sensitivity to MEK inhibition are CUP common features.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/4477922c33134d2989690669cbc5e8c0Test