TY - JOUR
T1 - Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma
AU - Mehrotra, Meenakshi
AU - Medeiros, L. Jeffrey
AU - Luthra, Rajyalakshmi
AU - Sargent, Rachel L.
AU - Yao, Hui
AU - Barkoh, Bedia A.
AU - Singh, Rajesh
AU - Patel, Keyur P.
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage characterized by uniform CD30 expression. The 2008 World Health Organization classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK)-positive (established entity) and ALK-negative (proposed new entity) ALCL. The genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly understood. In this study, we used microRNA microarray analysis to identify differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed significantly higher expression of miR-155 (0.888 ± 0.228) compared with ALK+ ALCL (0.0565 ± 0.009) on microarray and by quantitative real-time polymerase chain reaction in ALK- ALCL compared with ALK+ ALCL (P <.05) with a strong correlation between the 2 platforms (R = 0.9, P <.0003). A novel in situ hybridization method allows direct visualization of expression patterns and relative quantitation of miR-155 (mean score, 2.3 versus 1.3; P =.01) for the first time in tissue sections of ALCL. Among computationally predicted targets of miR-155, we identified ZNF652 (r = -0.57, P =.05), BACH1 (r = 0.88, P =.02), RBAK (r = 0.81, P =.05), TRIM32 (r = 0.92, P =.01), E2F2 (r = 0.81, P =.05), and TP53INP1 (r = -0.31, P =.03) as genes whose expression by quantitative real-time polymerase chain reaction correlated significantly with the level of miR-155 in ALCL tumor tissue.
AB - Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage characterized by uniform CD30 expression. The 2008 World Health Organization classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK)-positive (established entity) and ALK-negative (proposed new entity) ALCL. The genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly understood. In this study, we used microRNA microarray analysis to identify differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed significantly higher expression of miR-155 (0.888 ± 0.228) compared with ALK+ ALCL (0.0565 ± 0.009) on microarray and by quantitative real-time polymerase chain reaction in ALK- ALCL compared with ALK+ ALCL (P <.05) with a strong correlation between the 2 platforms (R = 0.9, P <.0003). A novel in situ hybridization method allows direct visualization of expression patterns and relative quantitation of miR-155 (mean score, 2.3 versus 1.3; P =.01) for the first time in tissue sections of ALCL. Among computationally predicted targets of miR-155, we identified ZNF652 (r = -0.57, P =.05), BACH1 (r = 0.88, P =.02), RBAK (r = 0.81, P =.05), TRIM32 (r = 0.92, P =.01), E2F2 (r = 0.81, P =.05), and TP53INP1 (r = -0.31, P =.03) as genes whose expression by quantitative real-time polymerase chain reaction correlated significantly with the level of miR-155 in ALCL tumor tissue.
KW - Anaplastic large cell lymphoma
KW - Expression profiling
KW - In situ hybridization
KW - RT-PCR
KW - microRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=84908220408&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2014.06.012
DO - 10.1016/j.humpath.2014.06.012
M3 - Article
C2 - 25128227
AN - SCOPUS:84908220408
SN - 0046-8177
VL - 45
SP - 1995
EP - 2005
JO - Human Pathology
JF - Human Pathology
IS - 10
ER -