| Title: |
Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study |
| Authors: |
UCL - SSS/IREC/PEDI - Pôle de Pédiatrie; UCL - SSS/IREC/SLUC - Pôle St.-Luc; UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique; UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique; Ercan, Ayse Bahar; Aronson, Melyssa; Fernandez, Nicholas R; Chang, Yuan; Levine, Adrian; Liu, Zhihui Amy; Negm, Logine; Edwards, Melissa; Bianchi, Vanessa; Stengs, Lucie; Chung, Jiil; Al-Battashi, Abeer; Reschke, Agnes; Lion, Alex; Ahmad, Alia; Lassaletta, Alvaro; Reddy, Alyssa T; Al-Darraji, Amir F; Shah, Amish C; Van Damme, An; Bendel, Anne; Rashid, Aqeela; Margol, Ashley S; Kelly, Bethany L; Pencheva, Bojana; Heald, Brandie; Lemieux-Anglin, Brianna; Crooks, Bruce; Koschmann, Carl; Gilpin, Catherine; Porter, Christopher C; Gass, David; Samuel, David; Ziegler, David S; Blumenthal, Deborah T; Kuo, Dennis John; Hamideh, Dima; Basel, Donald; Khuong-Quang, Dong-Anh; Stearns, Duncan; Opocher, Enrico; Carceller, Fernando; Baris Feldman, Hagit; Toledano, Helen; Winer, Ira; Scheers, Isabelle; Fedorakova, Ivana; Su, Jack M; Vengoechea, Jaime; Sterba, Jaroslav; Knipstein, Jeffrey; Hansford, Jordan R; Gonzales-Santos, Julieta Rita; Bhatia, Kanika; Bielamowicz, Kevin J; Minhas, Khurram; Nichols, Kim E; Cole, Kristina A; Penney, Lynette; Hjort, Magnus Aasved; Sabel, Magnus; Gil-da-Costa, Maria Joao; Murray, Matthew J; Miller, Matthew; Blundell, Maude L; Massimino, Maura; Al-Hussaini, Maysa; Al-Jadiry, Mazin F; Comito, Melanie A; Osborn, Michael; Link, Michael P; Zapotocky, Michal; Ghalibafian, Mithra; Shaheen, Najma; Mushtaq, Naureen; Waespe, Nicolas; Hijiya, Nobuko; Fuentes-Bolanos, Noemi; Ahmad, Olfat; Chamdine, Omar; Roy, Paromita; Pichurin, Pavel N; Nyman, Per; Pearlman, Rachel; Auer, Rebecca C; Sukumaran, Reghu K; Kebudi, Rejin; Dvir, Rina; Raphael, Robert; Elhasid, Ronit; McGee, Rose B; Chami, Rose; Noss, Ryan; Tanaka, Ryuma; Raskin, Salmo; Sen, Santanu; Lindhorst, Scott; Perreault, Sebastien; Caspi, Shani; Riaz, Shazia; Constantini, Shlomi; Albert, Sophie; Chaleff, Stanley; Bielack, Stefan; Chiaravalli, Stefano; Cramer, Stuart Louis; Roy, Sumita; Cahn, Suzanne; Penna, Suzanne; Hamid, Syed Ahmer; Ghafoor, Tariq; Imam, Uzma; Larouche, Valerie; Magimairajan Issai, Vanan; Foulkes, William D; Lee, Yi Yen; Nathan, Paul C; Maruvka, Yosef E; Greer, Mary-Louise C; Durno, Carol; Shlien, Adam; Ertl-Wagner, Birgit; Villani, Anita; Malkin, David; Hawkins, Cynthia; Bouffet, Eric; Das, Anirban; Tabori, Uri |
| Source: |
The Lancet. Oncology, Vol. 25, no. 5, p. 668-682 (2024) |
| Publisher Information: |
Lancet Pub. Group 2024 |
| Document Type: |
Electronic Resource |
| Abstract: |
BACKGROUND: 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. METHODS: 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. FINDINGS: 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 |
| Index Terms: |
info:eu-repo/semantics/article |
| URL: |
http://hdl.handle.net/2078.1/288016 |
| Availability: |
Open access content. Open access content; info:eu-repo/semantics/openAccess |
| Note: |
English |
| Other Numbers: |
UCDLC oai:dial.uclouvain.be:boreal:288016; boreal:288016; info:doi/10.1016/s1470-2045(24)00026-3; info:pmid/; urn:ISSN:1470-2045; urn:EISSN:1474-5488; 1508049802 |
| Contributing Source: |
UNIVERSITE CATHOLIQUE DE LOUVAIN; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1508049802 |
| Database: |
OAIster |