Non-coding recurrent mutations in chronic lymphocytic leukaemia

Xose S. Puente; Silvia Beà; Rafael Valdés-Mas; Neus Villamor; Jesús Gutiérrez-Abril; José I. Martín-Subero; Marta Munar; Carlota Rubio-Pérez; Pedro Jares; Marta Aymerich; Tycho Baumann; Renée Beekman; Laura Belver; Anna Carrio; Giancarlo Castellano; Guillem Clot; Enrique Colado; Dolors Colomer; Dolors Costa; Julio Delgado; Anna Enjuanes; Xavier Estivill; Adolfo A. Ferrando; Josep L. Gelpí; Blanca González; Santiago González; Marcos González; Marta Gut; Jesús M. Hernández-Rivas; Mónica López-Guerra; David Martín-García; Alba Navarro; Pilar Nicolás; Modesto Orozco; Ángel R. Payer; Magda Pinyol; David G. Pisano; Diana A. Puente; Ana C. Queirós; Víctor Quesada; Carlos M. Romeo-Casabona; Cristina Royo; Romina Royo; María Rozman; Nuria Russiñol; Itziar Salaverría; Kostas Stamatopoulos; Hendrik G. Stunnenberg; David Tamborero; María J. Terol; Alfonso Valencia; Nuria López-Bigas; David Torrents; Ivo Gut; Armando López-Guillermo; Carlos López-Otín; Elías Campo

doi:10.1038/nature14666

Non-coding recurrent mutations in chronic lymphocytic leukaemia

Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril, José I. Martín-Subero, Marta Munar, Carlota Rubio-Pérez, Pedro Jares, Marta Aymerich, Tycho Baumann, Renée Beekman, Laura Belver, Anna Carrio, Giancarlo Castellano, Guillem Clot, Enrique Colado, Dolors Colomer, Dolors Costa, Julio DelgadoAnna Enjuanes, Xavier Estivill, Adolfo A. Ferrando, Josep L. Gelpí, Blanca González, Santiago González, Marcos González, Marta Gut, Jesús M. Hernández-Rivas, Mónica López-Guerra, David Martín-García, Alba Navarro, Pilar Nicolás, Modesto Orozco, Ángel R. Payer, Magda Pinyol, David G. Pisano, Diana A. Puente, Ana C. Queirós, Víctor Quesada, Carlos M. Romeo-Casabona, Cristina Royo, Romina Royo, María Rozman, Nuria Russiñol, Itziar Salaverría, Kostas Stamatopoulos, Hendrik G. Stunnenberg, David Tamborero, María J. Terol, Alfonso Valencia, Nuria López-Bigas, David Torrents, Ivo Gut, Armando López-Guillermo, Carlos López-Otín, Elías Campo

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3′ region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥ 4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.

Originele taal-2	Engels
Pagina's (van-tot)	519-524
Aantal pagina's	6
Tijdschrift	Nature
Volume	526
Nummer van het tijdschrift	7574
DOI's	https://doi.org/10.1038/nature14666
Status	Gepubliceerd - 22 okt. 2015
Extern gepubliceerd	Ja

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Puente, X. S., Beà, S., Valdés-Mas, R., Villamor, N., Gutiérrez-Abril, J., Martín-Subero, J. I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., Baumann, T., Beekman, R., Belver, L., Carrio, A., Castellano, G., Clot, G., Colado, E., Colomer, D., Costa, D., ... Campo, E. (2015). Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature, 526(7574), 519-524. https://doi.org/10.1038/nature14666

@article{ba9efd33ce654de2b073d90680a9f882,

title = "Non-coding recurrent mutations in chronic lymphocytic leukaemia",

abstract = "Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3′ region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥ 4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.",

author = "Puente, {Xose S.} and Silvia Be{\`a} and Rafael Vald{\'e}s-Mas and Neus Villamor and Jes{\'u}s Guti{\'e}rrez-Abril and Mart{\'i}n-Subero, {Jos{\'e} I.} and Marta Munar and Carlota Rubio-P{\'e}rez and Pedro Jares and Marta Aymerich and Tycho Baumann and Ren{\'e}e Beekman and Laura Belver and Anna Carrio and Giancarlo Castellano and Guillem Clot and Enrique Colado and Dolors Colomer and Dolors Costa and Julio Delgado and Anna Enjuanes and Xavier Estivill and Ferrando, {Adolfo A.} and Gelp{\'i}, {Josep L.} and Blanca Gonz{\'a}lez and Santiago Gonz{\'a}lez and Marcos Gonz{\'a}lez and Marta Gut and Hern{\'a}ndez-Rivas, {Jes{\'u}s M.} and M{\'o}nica L{\'o}pez-Guerra and David Mart{\'i}n-Garc{\'i}a and Alba Navarro and Pilar Nicol{\'a}s and Modesto Orozco and Payer, {{\'A}ngel R.} and Magda Pinyol and Pisano, {David G.} and Puente, {Diana A.} and Queir{\'o}s, {Ana C.} and V{\'i}ctor Quesada and Romeo-Casabona, {Carlos M.} and Cristina Royo and Romina Royo and Mar{\'i}a Rozman and Nuria Russi{\~n}ol and Itziar Salaverr{\'i}a and Kostas Stamatopoulos and Stunnenberg, {Hendrik G.} and David Tamborero and Terol, {Mar{\'i}a J.} and Alfonso Valencia and Nuria L{\'o}pez-Bigas and David Torrents and Ivo Gut and Armando L{\'o}pez-Guillermo and Carlos L{\'o}pez-Ot{\'i}n and El{\'i}as Campo",

year = "2015",

month = oct,

day = "22",

doi = "10.1038/nature14666",

language = "English",

volume = "526",

pages = "519--524",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7574",

}

Puente, XS, Beà, S, Valdés-Mas, R, Villamor, N, Gutiérrez-Abril, J, Martín-Subero, JI, Munar, M, Rubio-Pérez, C, Jares, P, Aymerich, M, Baumann, T, Beekman, R, Belver, L, Carrio, A, Castellano, G, Clot, G, Colado, E, Colomer, D, Costa, D, Delgado, J, Enjuanes, A, Estivill, X, Ferrando, AA, Gelpí, JL, González, B, González, S, González, M, Gut, M, Hernández-Rivas, JM, López-Guerra, M, Martín-García, D, Navarro, A, Nicolás, P, Orozco, M, Payer, ÁR, Pinyol, M, Pisano, DG, Puente, DA, Queirós, AC, Quesada, V, Romeo-Casabona, CM, Royo, C, Royo, R, Rozman, M, Russiñol, N, Salaverría, I, Stamatopoulos, K, Stunnenberg, HG, Tamborero, D, Terol, MJ, Valencia, A, López-Bigas, N, Torrents, D, Gut, I, López-Guillermo, A, López-Otín, C & Campo, E 2015, 'Non-coding recurrent mutations in chronic lymphocytic leukaemia', Nature, vol. 526, nr. 7574, blz. 519-524. https://doi.org/10.1038/nature14666

TY - JOUR

T1 - Non-coding recurrent mutations in chronic lymphocytic leukaemia

AU - Puente, Xose S.

AU - Beà, Silvia

AU - Valdés-Mas, Rafael

AU - Villamor, Neus

AU - Gutiérrez-Abril, Jesús

AU - Martín-Subero, José I.

AU - Munar, Marta

AU - Rubio-Pérez, Carlota

AU - Jares, Pedro

AU - Aymerich, Marta

AU - Baumann, Tycho

AU - Beekman, Renée

AU - Belver, Laura

AU - Carrio, Anna

AU - Castellano, Giancarlo

AU - Clot, Guillem

AU - Colado, Enrique

AU - Colomer, Dolors

AU - Costa, Dolors

AU - Delgado, Julio

AU - Enjuanes, Anna

AU - Estivill, Xavier

AU - Ferrando, Adolfo A.

AU - Gelpí, Josep L.

AU - González, Blanca

AU - González, Santiago

AU - González, Marcos

AU - Gut, Marta

AU - Hernández-Rivas, Jesús M.

AU - López-Guerra, Mónica

AU - Martín-García, David

AU - Navarro, Alba

AU - Nicolás, Pilar

AU - Orozco, Modesto

AU - Payer, Ángel R.

AU - Pinyol, Magda

AU - Pisano, David G.

AU - Puente, Diana A.

AU - Queirós, Ana C.

AU - Quesada, Víctor

AU - Romeo-Casabona, Carlos M.

AU - Royo, Cristina

AU - Royo, Romina

AU - Rozman, María

AU - Russiñol, Nuria

AU - Salaverría, Itziar

AU - Stamatopoulos, Kostas

AU - Stunnenberg, Hendrik G.

AU - Tamborero, David

AU - Terol, María J.

AU - Valencia, Alfonso

AU - López-Bigas, Nuria

AU - Torrents, David

AU - Gut, Ivo

AU - López-Guillermo, Armando

AU - López-Otín, Carlos

AU - Campo, Elías

PY - 2015/10/22

Y1 - 2015/10/22

N2 - Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3′ region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥ 4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.

AB - Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3′ region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥ 4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.

UR - http://www.scopus.com/inward/record.url?scp=84945248976&partnerID=8YFLogxK

U2 - 10.1038/nature14666

DO - 10.1038/nature14666

M3 - Article

C2 - 26200345

AN - SCOPUS:84945248976

SN - 0028-0836

VL - 526

SP - 519

EP - 524

JO - Nature

JF - Nature

IS - 7574

ER -

Non-coding recurrent mutations in chronic lymphocytic leukaemia

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