Landscape of somatic mutations and clonal evolution in mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.

Type: Whole Genome Sequencing
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001000667	None	Illumina HiSeq 2000	72

Publications	Citations
Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Beà S, Valdés-Mas R, Navarro A, Salaverria I, Martín-Garcia D, Jares P, Giné E, Pinyol M, Royo C, Nadeu F, Conde L, Juan M, Clot G, Vizán P, Di Croce L, Puente DA, López-Guerra M, Moros A, Roue G, Aymerich M, Villamor N, Colomo L, Martínez A, Valera A, Martín-Subero JI, Amador V, Hernández L, Rozman M, Enjuanes A, Forcada P, Muntañola A, Hartmann EM, Calasanz MJ, Rosenwald A, Ott G, Hernández-Rivas JM, Klapper W, Siebert R, Wiestner A, Wilson WH, Colomer D, López-Guillermo A, López-Otín C, Puente XS, Campo E. Proc Natl Acad Sci U S A 110: 2013 18250-18255	323
IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms. Nadeu F, Mas-de-Les-Valls R, Navarro A, Royo R, Martín S, Villamor N, Suárez-Cisneros H, Mares R, Lu J, Enjuanes A, Rivas-Delgado A, Aymerich M, Baumann T, Colomer D, Delgado J, Morin RD, Zenz T, Puente XS, Campbell PJ, Beà S, Maura F, Campo E. Nat Commun 11: 2020 3390	23

Publications

Citations

Landscape of somatic mutations and clonal evolution in mantle cell lymphoma.
Beà S, Valdés-Mas R, Navarro A, Salaverria I, Martín-Garcia D, Jares P, Giné E, Pinyol M, Royo C, Nadeu F, Conde L, Juan M, Clot G, Vizán P, Di Croce L, Puente DA, López-Guerra M, Moros A, Roue G, Aymerich M, Villamor N, Colomo L, Martínez A, Valera A, Martín-Subero JI, Amador V, Hernández L, Rozman M, Enjuanes A, Forcada P, Muntañola A, Hartmann EM, Calasanz MJ, Rosenwald A, Ott G, Hernández-Rivas JM, Klapper W, Siebert R, Wiestner A, Wilson WH, Colomer D, López-Guillermo A, López-Otín C, Puente XS, Campo E. Proc Natl Acad Sci U S A 110: 2013 18250-18255

323

IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms.
Nadeu F, Mas-de-Les-Valls R, Navarro A, Royo R, Martín S, Villamor N, Suárez-Cisneros H, Mares R, Lu J, Enjuanes A, Rivas-Delgado A, Aymerich M, Baumann T, Colomer D, Delgado J, Morin RD, Zenz T, Puente XS, Campbell PJ, Beà S, Maura F, Campo E. Nat Commun 11: 2020 3390