المؤلفون: Chen, JP, Diekmann, C, Wu, HG, Chen, C, Della Chiara, G, Berrino, E, Georgiadis, KL, Bouwman, BAM, Virdi, M, Harbers, L, Bellomo, SE, Marchio, C, Bienko, M, Crosetto, N

المصدر: Nature communications. 15(1):1768

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:155028008Test

المؤلفون: Zhang, N., Harbers, L., Simonetti, M., Diekmann, C., Verron, Q., Berrino, E., Bellomo, S.E., Longo, G.M.C., Ratz, M., Schultz, N., Tarish, F., Su, P., Han, B., Wang, W., Onorato, S., Grassini, D., Ballarino, R., Giordano, S., Yang, Q., Sapino, A., Frisén, J., Alkass, K., Druid, H., Roukos, V., Helleday, T., Marchiò, C., Bienko, M., Crosetto, N.

الوصف: 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: text

العلاقة: https://eprints.whiterose.ac.uk/213302/1/s41467-024-47664-z.pdfTest; Zhang, N., Harbers, L. orcid.org/0000-0003-3910-6497 , Simonetti, M. orcid.org/0000-0003-3322-1697 et al. (25 more authors) (2024) High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue. Nature Communications, 15. 3475. ISSN 2041-1723

الإتاحة: https://doi.org/10.1038/s41467-024-47664-zTest
https://eprints.whiterose.ac.uk/213302Test/
https://eprints.whiterose.ac.uk/213302/1/s41467-024-47664-z.pdfTest

المؤلفون: Annaratone, L, Simonetti, M, Wernersson, E, Marchio, C, Garnerone, S, Scalzo, MS, Bienko, M, Chiarle, R, Sapino, A, Crosetto, N

المصدر: Oncotarget. 8(12):18680-18698

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:135360037Test

المؤلفون: Berrino, E, Annaratone, L, Bellomo, SE, Ferrero, G, Gagliardi, A, Bragoni, A, Grassini, D, Guarrera, S, Parlato, C, Casorzo, L, Panero, M, Sarotto, I, Giordano, S, Cereda, M, Montemurro, F, Ponzone, R, Crosetto, N, Naccarati, A, Sapino, A, Marchio, C

المصدر: Genome medicine. 14(1):98

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:150606979Test

المؤلفون: Stella G. M., Marchio C., Bari E., Ferrarotti I., Bertuccio F. R., Di Gennaro A., Abbott D. M., Putignano P., Campo I., Torre M. L., Corsico A. G.

المساهمون: Stella, G. M., Marchio, C., Bari, E., Ferrarotti, I., Bertuccio, F. R., Di Gennaro, A., Abbott, D. M., Putignano, P., Campo, I., Torre, M. L., Corsico, A. G.

مصطلحات موضوعية: genetic, malignant pleural mesothelioma, microenvironment, targeted therapies

الوصف: MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36834912; info:eu-repo/semantics/altIdentifier/wos/WOS:000938522100001; volume:24; issue:4; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; https://hdl.handle.net/11579/150663Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85149052886

الإتاحة: https://doi.org/10.3390/ijms24043496Test
https://hdl.handle.net/11579/150663Test

المؤلفون: Cserni B., Kilmartin D., O’Loughlin M., Andreu X., Bagó-Horváth Z., Bianchi S., Chmielik E., Figueiredo P., Floris G., Foschini M. P., Kovács A., Heikkilä P., Kulka J., Laenkholm A. V., Liepniece-Karele I., Marchiò C., Provenzano E., Regitnig P., Reiner A., Ryška A., Sapino A., Stovgaard E. S., Quinn C., Zolota V., Webber M., Glynn S. A., Bori R., Csörgő E., Oláh-Németh O., Pancsa T., Sejben A., Sejben I., Vörös A., Zombori T., Nyári T., Callagy G., Cserni G.

المساهمون: Cserni B., Kilmartin D., O’Loughlin M., Andreu X., Bagó-Horváth Z., Bianchi S., Chmielik E., Figueiredo P., Floris G., Foschini M.P., Kovács A., Heikkilä P., Kulka J., Laenkholm A.V., Liepniece-Karele I., Marchiò C., Provenzano E., Regitnig P., Reiner A., Ryška A., Sapino A., Stovgaard E.S., Quinn C., Zolota V., Webber M., Glynn S.A., Bori R., Csörgő E., Oláh-Németh O., Pancsa T., Sejben A., Sejben I., Vörös A., Zombori T., Nyári T., Callagy G., Cserni G.

مصطلحات موضوعية: European Working Group for Breast Screening Pathology, ONEST, TIL, breast cancer, international immuno-oncology biomarker working group, observers needed to evaluate subjective test, reproducibility, sTIL, triple-negative, tumour-infiltrating lymphocytes

الوصف: Simple Summary Tumour-infiltrating lymphocytes (TILs) reflect the host's response against tumours. TILs have a strong prognostic effect in the so-called triple-negative (oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 negative) subset of breast cancers and predict a better response when primary systemic (neoadjuvant) treatment is administered. Although they are easy to assess, their quantitative assessment is subject to some inter-observer variation. ONEST (Observers Needed to Evaluate Subjective Tests) is a new way of analysing inter-observer variability and helps in estimating the number of observers required for a more reliable estimation of this phenomenon. This aspect of reproducibility for TILs has not been explored previously. Our analysis suggests that between six and nine pathologists can give a good approximation of inter-observer agreement in TIL assessments. Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36831541; info:eu-repo/semantics/altIdentifier/wos/WOS:000941465600001; volume:15; issue:4; firstpage:1199; lastpage:1210; numberofpages:12; journal:CANCERS; https://hdl.handle.net/11585/922277Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85149152852; https://www.mdpi.com/2072-6694/15/4/1199Test

الإتاحة: https://doi.org/10.3390/cancers15041199Test
https://hdl.handle.net/11585/922277Test
https://www.mdpi.com/2072-6694/15/4/1199Test

المؤلفون: Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., Tagliafico E.

المساهمون: Russo, A., Incorvaia, L., Capoluongo, E., Tagliaferri, P., Gori, S., Cortesi, L., Genuardi, M., Turchetti, D., De Giorgi, U., Di Maio, M., Barberis, M., Dessena, M., Del Re, M., Lapini, A., Luchini, C., Jereczek-Fossa, B. A., Sapino, A., Cinieri, S., Beretta, G., Bella, M. A., Bracarda, S., Colombo, N., Conteduca, V., Del Mastro, L., Galvano, A., Gristina, V., Guarneri, V., La Verde, N., Lorusso, D., Marchetti, P., Normanno, N., Ottini, L., Pensabene, M., Pignata, S., Procopio, G., Ricevuto, E., Silvestris, N., Tassone, P., Tucci, M., Donato, V., Carrara, S., Paiella, S., Gentilini, O., Gunelli, R., Nicolis, F., Buttitta, F., Colecchia, M., Fassan, M., Malapelle, U., Marchetti, A., Marchio, C., Scarpa, A., Truini, M., Zamboni, G., Gion, M., Trevisiol, C., Gronchi, A., Danesi, R., Di Marco, V., Carrera, P., Ghiorzo, P., Pasini, B., Varesco, L., Artibani, W., Ludovico, G., Campanella, O., Vatrano, S., Tagliafico, E.

مصطلحات موضوعية: BRCA testing, BRCA-related cancer, BRCA1, BRCA2, genetic counseling, pancreatic ductal adenocarcinoma, PARP inhibitors

الوصف: Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35597177; info:eu-repo/semantics/altIdentifier/wos/WOS:000806761000001; volume:7; issue:3; journal:ESMO OPEN; https://hdl.handle.net/20.500.11768/152865Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85130700050; https://www.esmoopen.com/article/S2059-7029Test(22)00077-1/fulltext

الإتاحة: https://doi.org/20.500.11768/152865Test
https://doi.org/10.1016/j.esmoop.2022.100459Test
https://hdl.handle.net/20.500.11768/152865Test
https://www.esmoopen.com/article/S2059-7029Test(22)00077-1/fulltext

المؤلفون: Garutti M., Griguolo G., Botticelli A., Buzzatti G., De Angelis C., Gerratana L., Molinelli C., Adamo V., Bianchini G., Biganzoli L., Curigliano G., De Laurentiis M., Fabi A., Frassoldati A., Gennari A., Marchio C., Perrone F., Viale G., Zamagni C., Zambelli A., Del Mastro L., De Placido S., Guarneri V., Marchetti P., Puglisi F.

المساهمون: Garutti, M., Griguolo, G., Botticelli, A., Buzzatti, G., De Angelis, C., Gerratana, L., Molinelli, C., Adamo, V., Bianchini, G., Biganzoli, L., Curigliano, G., De Laurentiis, M., Fabi, A., Frassoldati, A., Gennari, A., Marchio, C., Perrone, F., Viale, G., Zamagni, C., Zambelli, A., Del Mastro, L., De Placido, S., Guarneri, V., Marchetti, P., Puglisi, F.

مصطلحات موضوعية: adjuvant, breast cancer, chemotherapy, consensu, ctDNA, endocrine therapy, genomic signature, hormone receptor, risk of relapse, TNM

الوصف: Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. During the past three decades, several improvements in the adjuvant treatment of hormone receptor-positive/HER2−negative breast cancer have been achieved with the introduction of optimized adjuvant chemotherapy and endocrine treatment. However, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (hIGh Risk DEfinition in breast cancer) working group was established with the aim of reviewing evidence from the literature to synthesize the current relevant features that predict hormonepositive/HER2−negative early breast cancer relapse. A panel of experts in breast cancer was involved in identifying clinical, pathological, morphological, and genetic factors. A RAND consensus method was used to define the relevance of each risk factor. Among the 21 features included, 12 were considered relevant risk factors for relapse. For each of these, we provided a consensus statement and relevant comments on the supporting scientific evidence. This work may guide clinicians in the practical management of hormone-positive/HER2−negative early breast cancers.

العلاقة: volume:14; issue:8; firstpage:1898; journal:CANCERS; http://hdl.handle.net/11390/1224377Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85127791037

الإتاحة: https://doi.org/10.3390/cancers14081898Test
http://hdl.handle.net/11390/1224377Test

المؤلفون: Berrino E., Filippi R., Visintin C., Peirone S., Fenocchio E., Farinea G., Veglio F., Aglietta M., Sapino A., Cereda M., Visintin R., Pasini B., Marchio' C.

المساهمون: Berrino E., Filippi R., Visintin C., Peirone S., Fenocchio E., Farinea G., Veglio F., Aglietta M., Sapino A., Cereda M., Visintin R., Pasini B., Marchio' C.

الوصف: 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.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35260767; info:eu-repo/semantics/altIdentifier/wos/WOS:000766166400001; volume:6; issue:1; firstpage:15; lastpage:23; numberofpages:9; journal:NPJ PRECISION ONCOLOGY; http://hdl.handle.net/2318/1851481Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85126245417; https://www.nature.com/articles/s41698-022-00258-8Test

الإتاحة: https://doi.org/10.1038/s41698-022-00258-8Test
http://hdl.handle.net/2318/1851481Test
https://www.nature.com/articles/s41698-022-00258-8Test

المؤلفون: Metovic J., Cascardi E., Uccella S., Maragliano R., Querzoli G., Osella-Abate S., Pittaro A., La Rosa S., Bogina G., Cassoni P., Marchio C., Sapino A., Castellano I., Papotti M.

المساهمون: Metovic, J., Cascardi, E., Uccella, S., Maragliano, R., Querzoli, G., Osella-Abate, S., Pittaro, A., La Rosa, S., Bogina, G., Cassoni, P., Marchio, C., Sapino, A., Castellano, I., Papotti, M.

مصطلحات موضوعية: Breast cancer, Diagnosi, NEC, NET, Neuroendocrine, WHO 2019

الوصف: The classification of breast neuroendocrine neoplasms (Br-NENs) was modified many times over the years and is still a matter of discussion. In the present study, we aimed to evaluate the diagnostic reproducibility and impact on patient outcomes of the most recent WHO 2019 edition of breast tumor classification, namely, for neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). This multicentric observational study included 287 breast neoplasms with NE differentiation. The cases were blindly classified by three independent groups of dedicated breast and/or endocrine pathologists following the 2019 guidelines. Diagnostic concordance and clinical impact were assessed. We observed only a moderate overall diagnostic agreement across the three centers (Cohen’s kappa 0.4532) in distinguishing NET from solid papillary carcinomas (SPCs) and no special type carcinomas (NST) with NE differentiation. Br-NENs were diagnosed in 122/287 (42.5%) cases, subclassified as 11 NET G1 (3.8%), 84 NET G2 (29.3%), and 27 NEC (9.4%), the latter group consisting of 26 large-cell and 1 small-cell NECs. The remaining 165/287 (57.5%) cases were labeled as non-NEN, including SPC, mucinous, NST, and mixed NE carcinomas. While NET and non-NEN cases had a comparable outcome, the diagnosis of NECs showed negative impact on disease-free interval compared to NETs and non-NENs (p = 0.0109). In conclusion, the current diagnostic classification of Br-NENs needs further adjustments regarding morphological and immunohistochemical criteria to increase the diagnostic reproducibility among pathologists. Our data suggest that, apart from high-grade small- and large-cell NECs, Br-NENs behave like non-NEN breast carcinomas and should be managed similarly.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36243799; info:eu-repo/semantics/altIdentifier/wos/WOS:000869192300001; volume:481; issue:6; firstpage:839; lastpage:846; numberofpages:8; journal:VIRCHOWS ARCHIV; https://hdl.handle.net/11383/2142451Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85139908395

الإتاحة: https://doi.org/10.1007/s00428-022-03426-0Test
https://hdl.handle.net/11383/2142451Test