Sökning: WFRF:(Costa Enrico) > Clinical and biolog...
Fältnamn | Indikatorer | Metadata |
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000 | 10998naa a2202209 4500 | |
001 | oai:gup.ub.gu.se/338586 | |
003 | SwePub | |
008 | 240719s2024 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/3385862 URI |
024 | 7 | a https://doi.org/10.1016/S1470-2045(24)00026-32 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Ercan, Ayse Bahar4 aut |
245 | 1 0 | a Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study. |
264 | 1 | c 2024 |
520 | a Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng |
653 | a Humans | |
653 | a Male | |
653 | a Female | |
653 | a Child | |
653 | a Child | |
653 | a Preschool | |
653 | a Neoplastic Syndromes | |
653 | a Hereditary | |
653 | a genetics | |
653 | a therapy | |
653 | a Cross-Sectional Studies | |
653 | a Adolescent | |
653 | a Brain Neoplasms | |
653 | a genetics | |
653 | a therapy | |
653 | a mortality | |
653 | a pathology | |
653 | a epidemiology | |
653 | a DNA Mismatch Repair | |
653 | a Longitudinal Studies | |
653 | a Colorectal Neoplasms | |
653 | a genetics | |
653 | a pathology | |
653 | a mortality | |
653 | a Incidence | |
653 | a MutS Homolog 2 Protein | |
653 | a genetics | |
653 | a MutL Protein Homolog 1 | |
653 | a genetics | |
653 | a Adult | |
653 | a Young Adult | |
653 | a Mutation | |
653 | a DNA-Binding Proteins | |
700 | 1 | a Aronson, Melyssa4 aut |
700 | 1 | a Fernandez, Nicholas R4 aut |
700 | 1 | a Chang, Yuan4 aut |
700 | 1 | a Levine, Adrian4 aut |
700 | 1 | a Liu, Zhihui Amy4 aut |
700 | 1 | a Negm, Logine4 aut |
700 | 1 | a Edwards, Melissa4 aut |
700 | 1 | a Bianchi, Vanessa4 aut |
700 | 1 | a Stengs, Lucie4 aut |
700 | 1 | a Chung, Jiil4 aut |
700 | 1 | a Al-Battashi, Abeer4 aut |
700 | 1 | a Reschke, Agnes4 aut |
700 | 1 | a Lion, Alex4 aut |
700 | 1 | a Ahmad, Alia4 aut |
700 | 1 | a Lassaletta, Alvaro4 aut |
700 | 1 | a Reddy, Alyssa T4 aut |
700 | 1 | a Al-Darraji, Amir F4 aut |
700 | 1 | a Shah, Amish C4 aut |
700 | 1 | a Van Damme, An4 aut |
700 | 1 | a Bendel, Anne4 aut |
700 | 1 | a Rashid, Aqeela4 aut |
700 | 1 | a Margol, Ashley S4 aut |
700 | 1 | a Kelly, Bethany L4 aut |
700 | 1 | a Pencheva, Bojana4 aut |
700 | 1 | a Heald, Brandie4 aut |
700 | 1 | a Lemieux-Anglin, Brianna4 aut |
700 | 1 | a Crooks, Bruce4 aut |
700 | 1 | a Koschmann, Carl4 aut |
700 | 1 | a Gilpin, Catherine4 aut |
700 | 1 | a Porter, Christopher C4 aut |
700 | 1 | a Gass, David4 aut |
700 | 1 | a Samuel, David4 aut |
700 | 1 | a Ziegler, David S4 aut |
700 | 1 | a Blumenthal, Deborah T4 aut |
700 | 1 | a Kuo, Dennis John4 aut |
700 | 1 | a Hamideh, Dima4 aut |
700 | 1 | a Basel, Donald4 aut |
700 | 1 | a Khuong-Quang, Dong-Anh4 aut |
700 | 1 | a Stearns, Duncan4 aut |
700 | 1 | a Opocher, Enrico4 aut |
700 | 1 | a Carceller, Fernando4 aut |
700 | 1 | a Baris Feldman, Hagit4 aut |
700 | 1 | a Toledano, Helen4 aut |
700 | 1 | a Winer, Ira4 aut |
700 | 1 | a Scheers, Isabelle4 aut |
700 | 1 | a Fedorakova, Ivana4 aut |
700 | 1 | a Su, Jack M4 aut |
700 | 1 | a Vengoechea, Jaime4 aut |
700 | 1 | a Sterba, Jaroslav4 aut |
700 | 1 | a Knipstein, Jeffrey4 aut |
700 | 1 | a Hansford, Jordan R4 aut |
700 | 1 | a Gonzales-Santos, Julieta Rita4 aut |
700 | 1 | a Bhatia, Kanika4 aut |
700 | 1 | a Bielamowicz, Kevin J4 aut |
700 | 1 | a Minhas, Khurram4 aut |
700 | 1 | a Nichols, Kim E4 aut |
700 | 1 | a Cole, Kristina A4 aut |
700 | 1 | a Penney, Lynette4 aut |
700 | 1 | a Hjort, Magnus Aasved4 aut |
700 | 1 | a Sabel, Magnus,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics4 aut0 (Swepub:gu)xsabma |
700 | 1 | a Gil-da-Costa, Maria Joao4 aut |
700 | 1 | a Murray, Matthew J4 aut |
700 | 1 | a Miller, Matthew4 aut |
700 | 1 | a Blundell, Maude L4 aut |
700 | 1 | a Massimino, Maura4 aut |
700 | 1 | a Al-Hussaini, Maysa4 aut |
700 | 1 | a Al-Jadiry, Mazin F4 aut |
700 | 1 | a Comito, Melanie A4 aut |
700 | 1 | a Osborn, Michael4 aut |
700 | 1 | a Link, Michael P4 aut |
700 | 1 | a Zapotocky, Michal4 aut |
700 | 1 | a Ghalibafian, Mithra4 aut |
700 | 1 | a Shaheen, Najma4 aut |
700 | 1 | a Mushtaq, Naureen4 aut |
700 | 1 | a Waespe, Nicolas4 aut |
700 | 1 | a Hijiya, Nobuko4 aut |
700 | 1 | a Fuentes-Bolanos, Noemi4 aut |
700 | 1 | a Ahmad, Olfat4 aut |
700 | 1 | a Chamdine, Omar4 aut |
700 | 1 | a Roy, Paromita4 aut |
700 | 1 | a Pichurin, Pavel N4 aut |
700 | 1 | a Nyman, Per4 aut |
700 | 1 | a Pearlman, Rachel4 aut |
700 | 1 | a Auer, Rebecca C4 aut |
700 | 1 | a Sukumaran, Reghu K4 aut |
700 | 1 | a Kebudi, Rejin4 aut |
700 | 1 | a Dvir, Rina4 aut |
700 | 1 | a Raphael, Robert4 aut |
700 | 1 | a Elhasid, Ronit4 aut |
700 | 1 | a McGee, Rose B4 aut |
700 | 1 | a Chami, Rose4 aut |
700 | 1 | a Noss, Ryan4 aut |
700 | 1 | a Tanaka, Ryuma4 aut |
700 | 1 | a Raskin, Salmo4 aut |
700 | 1 | a Sen, Santanu4 aut |
700 | 1 | a Lindhorst, Scott4 aut |
700 | 1 | a Perreault, Sebastien4 aut |
700 | 1 | a Caspi, Shani4 aut |
700 | 1 | a Riaz, Shazia4 aut |
700 | 1 | a Constantini, Shlomi4 aut |
700 | 1 | a Albert, Sophie4 aut |
700 | 1 | a Chaleff, Stanley4 aut |
700 | 1 | a Bielack, Stefan4 aut |
700 | 1 | a Chiaravalli, Stefano4 aut |
700 | 1 | a Cramer, Stuart Louis4 aut |
700 | 1 | a Roy, Sumita4 aut |
700 | 1 | a Cahn, Suzanne4 aut |
700 | 1 | a Penna, Suzanne4 aut |
700 | 1 | a Hamid, Syed Ahmer4 aut |
700 | 1 | a Ghafoor, Tariq4 aut |
700 | 1 | a Imam, Uzma4 aut |
700 | 1 | a Larouche, Valerie4 aut |
700 | 1 | a Magimairajan Issai, Vanan4 aut |
700 | 1 | a Foulkes, William D4 aut |
700 | 1 | a Lee, Yi Yen4 aut |
700 | 1 | a Nathan, Paul C4 aut |
700 | 1 | a Maruvka, Yosef E4 aut |
700 | 1 | a Greer, Mary-Louise C4 aut |
700 | 1 | a Durno, Carol4 aut |
700 | 1 | a Shlien, Adam4 aut |
700 | 1 | a Ertl-Wagner, Birgit4 aut |
700 | 1 | a Villani, Anita4 aut |
700 | 1 | a Malkin, David4 aut |
700 | 1 | a Hawkins, Cynthia4 aut |
700 | 1 | a Bouffet, Eric4 aut |
700 | 1 | a Das, Anirban4 aut |
700 | 1 | a Tabori, Uri4 aut |
710 | 2 | a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för pediatrik4 org |
773 | 0 | t The Lancet Oncologyg 25:5, s. 668-682q 25:5<668-682x 1470-2045 |
856 | 4 8 | u https://gup.ub.gu.se/publication/338586 |
856 | 4 8 | u https://doi.org/10.1016/S1470-2045(24)00026-3 |
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