PMID- 32720348
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20210416
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 147
IP  - 10
DP  - 2020 Nov 15
TI  - Chronic lymphocytic leukemia patients with IGH translocations are characterized 
      by a distinct genetic landscape with prognostic implications.
PG  - 2780-2792
LID - 10.1002/ijc.33235 [doi]
AB  - Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy 
      chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). The 
      prognostic significance of the IGH translocation is controversial and its 
      mutational profile remains unknown. Here, we present for the first time a 
      comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with 
      IGH rearrangement (IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct 
      mutational profile with recurrent mutations in NOTCH1, IGLL5, POT1, BCL2, FBXW7, 
      ZMYM3, MGA, BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7 mutations were 
      significantly associated with this subgroup and almost half of BCL2, IGLL5 and 
      HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. 
      Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency 
      and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in 
      genes related to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to 
      first treatment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL 
      patients carrying 13q-, normal fluorescence in situ hybridization (FISH) and +12 
      CLL, being this prognosis particularly poor when NOTCH1, SF3B1, TP53, BIRC3 and 
      BRAF were also mutated. The presence of these mutations not only was an 
      independent risk factor within IGHR-CLLs, but also refined the prognosis of 
      low-risk cytogenetic patients (13q-/normal FISH). Hence, our study demonstrates 
      that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and 
      highlights the relevance of incorporating NGS and the status of IGH by FISH 
      analysis to refine the risk-stratification CLL model.
CI  - (c) 2020 Union for International Cancer Control.
FAU - Perez-Carretero, Claudia
AU  - Perez-Carretero C
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Hernandez-Sanchez, Maria
AU  - Hernandez-Sanchez M
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Gonzalez, Teresa
AU  - Gonzalez T
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Quijada-Alamo, Miguel
AU  - Quijada-Alamo M
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Martin-Izquierdo, Marta
AU  - Martin-Izquierdo M
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Hernandez-Sanchez, Jesus-Maria
AU  - Hernandez-Sanchez JM
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Vidal, Maria-Jesus
AU  - Vidal MJ
AD  - Servicio de Hematologia, Hospital Universitario, Leon, Spain.
FAU - de Coca, Alfonso Garcia
AU  - de Coca AG
AD  - Servicio de Hematologia, Hospital Clinico, Valladolid, Spain.
FAU - Aguilar, Carlos
AU  - Aguilar C
AD  - Servicio de Hematologia, Complejo Hospitalario de Soria, Soria, Spain.
FAU - Vargas-Pabon, Manuel
AU  - Vargas-Pabon M
AD  - Servicio de Hematologia, Hospital Jarrio, Asturias, Spain.
FAU - Alonso, Sara
AU  - Alonso S
AD  - Servicio de Hematologia, Hospital Universitario Central de Asturias, Oviedo, 
      Spain.
FAU - Sierra, Magdalena
AU  - Sierra M
AD  - Servicio de Hematologia, Hospital Virgen de la Concha, Zamora, Spain.
FAU - Rubio-Martinez, Araceli
AU  - Rubio-Martinez A
AD  - Servicio de Hematologia, Hospital Miguel Servet, Zaragoza, Spain.
FAU - Davila, Julio
AU  - Davila J
AD  - Servicio de Hematologia, Hospital Nuestra Senora de Sonsoles, Avila, Spain.
FAU - Diaz-Valdes, Jose R
AU  - Diaz-Valdes JR
AD  - Servicio de Hematologia, Hospital General de Segovia, Segovia, Spain.
FAU - Queizan, Jose-Antonio
AU  - Queizan JA
AD  - Servicio de Hematologia, Hospital General de Segovia, Segovia, Spain.
FAU - Hernandez-Rivas, Jose-Angel
AU  - Hernandez-Rivas JA
AD  - Servicio de Hematologia, Hospital Universitario Infanta Leonor, Universidad 
      Complutense, Madrid, Spain.
FAU - Benito, Rocio
AU  - Benito R
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Rodriguez-Vicente, Ana E
AU  - Rodriguez-Vicente AE
AUID- ORCID: 0000-0001-6516-2172
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
FAU - Hernandez-Rivas, Jesus-Maria
AU  - Hernandez-Rivas JM
AD  - Universidad de Salamanca, IBSAL, Centro de Investigacion del Cancer, IBMCC-CSIC, 
      Salamanca, Spain.
AD  - Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200904
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Immunoglobulin Heavy Chains)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosomes, Human, Pair 13/genetics
MH  - Chromosomes, Human, Pair 14/genetics
MH  - Female
MH  - *Gene Regulatory Networks
MH  - Genetic Predisposition to Disease
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - Immunoglobulin Heavy Chains/*genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Prognosis
MH  - Sequence Analysis, DNA
MH  - *Translocation, Genetic
OTO - NOTNLM
OT  - chromosomal translocations
OT  - chronic lymphocytic leukemia
OT  - clinical molecular genetics
OT  - cytogenetics
OT  - high-throughput sequencing
OT  - prognostic biomarkers
EDAT- 2020/07/29 06:00
MHDA- 2021/04/17 06:00
CRDT- 2020/07/29 06:00
PHST- 2020/01/16 00:00 [received]
PHST- 2020/06/19 00:00 [revised]
PHST- 2020/07/07 00:00 [accepted]
PHST- 2020/07/29 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2020/07/29 06:00 [entrez]
AID - 10.1002/ijc.33235 [doi]
PST - ppublish
SO  - Int J Cancer. 2020 Nov 15;147(10):2780-2792. doi: 10.1002/ijc.33235. Epub 2020 
      Sep 4.