Abstract B09: DNA polymerase mutations trigger rapid onset of ultra-hypermutant malignant brain tumors in children with biallelic mismatch repair deficiency

Abstract B09: DNA polymerase mutations trigger rapid onset of ultra-hypermutant malignant brain tumors in children with biallelic mismatch repair deficiency

Background: Biallelic Mismatch Repair Deficiency (bMMRD) is a childhood cancer predisposition syndrome caused by germline mutations in MSH2, MSH6, MLH1, and PMS2. The leading cause of death is malignant brain tumors. The genomic landscape and secondary somatic mutations of bMMRD brain tumors are unk...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2015-12, Vol.75 (23_Supplement), p.B09-B09
Hauptverfasser: Shlien, Adam, Campbell, Brittany B., Borja, Richard de, Alexandrov, Ludmil B., Merico, Daniele, Wedge, David, Loo, Peter Van, Tarpey, Patrick S., Coupland, Paul, Pollett, Aaron, Lipman, Tatiana, Heidari, Abolfazl, Deshmukh, Shriya, Gerstung, Moritz, Merino, Diana, Ramakrishna, Manasa, Remke, Marc, Arnold, Roland, Panigrahi, Gagan B., Afzal, Samina, Larouche, Valerie, Druker, Harriet, Lerner-Ellis, Jordan, Mistry, Matthew, Dvir, Rina, Grant, Ronald, Elhasid, Ronit, Farah, Roula, Taylor, Glenn P., Nathan, Paul C., Alexander, Sarah, Ben-Shachar, Shay, Jabado, Nada, Gallinger, Steven, Constantini, Shlohmi, Dirks, Peter, Huang, Annie, Scherer, Steven W., Grundy, Richard G., Durno, Carol, Aronson, Melyssa, Meyn, M Stephen, Taylor, Michael D., Pursell, Zachary F., Pearson, Christopher E., Malkin, David, Futreal, P Andrew, Hawkins, Cynthia, Bouffet, Eric, Campbell, Peter J., Tabori, Uri
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background: Biallelic Mismatch Repair Deficiency (bMMRD) is a childhood cancer predisposition syndrome caused by germline mutations in MSH2, MSH6, MLH1, and PMS2. The leading cause of death is malignant brain tumors. The genomic landscape and secondary somatic mutations of bMMRD brain tumors are unknown. Methods: We analyzed 27 cancers and corresponding normal tissues from bMMRD patients using genome, exome sequencing and SNP-arrays. Additionally, we performed sequential sequencing from five primary and recurrent tumor pairs. Results: BMMRD malignant brain tumors harbored massive numbers of substitution mutations (>250/Mb), greater than all childhood and most adult cancers (>7,000 analyzed). These cancers lacked copy number alterations (p
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.BRAIN15-B09