Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

被引：41

作者：

Forero-Castro, Maribel ^{[1
,2
]}

Robledo, Cristina ^{[1
]}

Benito, Rocio ^{[1
]}

Abaigar, Maria ^{[1
]}

Africa Martin, Ana ^{[1
,3
]}

Arefi, Maryam ^{[4
]}

Luis Fuster, Jose ^{[5
]}

de las Heras, Natalia ^{[6
]}

Rodriguez, Juan N. ^{[7
]}

Quintero, Jonathan ^{[8
]}

Riesco, Susana ^{[9
]}

Hermosin, Lourdes ^{[10
]}

de la Fuente, Ignacio ^{[11
]}

Recio, Isabel ^{[12
]}

Ribera, Jordi ^{[13
]}

Labrador, Jorge ^{[14
]}

Alonso, Jose M. ^{[15
]}

Olivier, Carmen ^{[16
]}

Sierra, Magdalena ^{[17
]}

Megido, Marta ^{[18
]}

Corchete-Sanchez, Luis A. ^{[3
]}

Ciudad Pizarro, Juana ^{[19
]}

Luis Garcia, Juan ^{[20
]}

Ribera, Jose M. ^{[14
]}

Hernandez-Rivas, Jesus M. ^{[1
,3
]}

机构：

[1] Univ Salamanca, CSIC, IBMCC, IBSAL,Canc Res Ctr, E-37008 Salamanca, Spain

[2] Pedag & Technol Univ Colombia UPTC, Sch Biol Sci GEBIMOL, Tunja, Colombia

[3] Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain

[4] Clin Univ Hosp Valladolid, Dept Hematol, Valladolid, Spain

[5] Clin Univ Hosp Virgen Arrixaca, Dept Pediat Oncohematol, Murcia, Spain

[6] Virgen Blanca Hosp, Dept Hematol, Leon, Spain

[7] Juan Raman Jimenez Hosp, Dept Hematol, Huelva, Spain

[8] Miguel Servet Hosp, Dept Hematol, Zaragoza, Spain

[9] Univ Hosp Salamanca, Dept Pediat Oncohematol, Salamanca, Spain

[10] Jerez Hosp, Jerez Frontera, Dept Hematol, Cadiz, Spain

[11] Rio Hortega Hosp, Dept Hematol, Valladolid, Spain

[12] Nuestra Senora Sonsoles Hosp, Dept Hematol, Avila, Spain

[13] Josep Carreras Res Inst, ICO Hosp Germans Trias & Pujol, Dept Hematol, Badalona, Spain

[14] Univ Hosp Burgos, Dept Hematol, Burgos, Spain

[15] Rio Carrion Hosp, Dept Hematol, Palencia, Spain

[16] Gen Hosp Segovia, Dept Hematol, Segovia, Spain

[17] Virgen Concha Hosp, Dept Hematol, Zamora, Spain

[18] Bierzo Hosp, Dept Hematol, Leon Ponferrada, Spain

[19] USAL, Cytometry Serv NUCLEUS Res Support Platform, Salamanca, Spain

[20] Inst Hlth Sci Studies Castile & Leon IESCYL, Salamanca, Spain

来源：

PLOS ONE | 2016年 / 11卷 / 02期

关键词：

CHEMOTHERAPY INCLUDING RITUXIMAB; MINIMAL RESIDUAL DISEASE; CONCERTED ACTION REPORT; CHROMOSOMAL REARRANGEMENTS; GLUCOCORTICOID RESISTANCE; PEDIATRIC DISEASE; CANCER GENOMES; CHROMOTHRIPSIS; HYBRIDIZATION; CHILDHOOD;

D O I：

10.1371/journal.pone.0148972

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good-or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.

引用

页数：20

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