Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.
Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of "clusters" of MYC genes. In this study, we sought to further characterize these clusters of MYC signals by determining whether the presence of these correlated with other genetic features, mRNA levels, protein, and overall survival. We found that MYC clusters correlated with an abnormal MYC locus and with increased mRNA. MYC mRNA correlated with protein levels, and both increased mRNA and protein correlated with poorer overall survival. MYC clusters were seen in both the germinal center and activated B-cell subtypes of DLBCL. Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance.
Department of Pathology, University of Arizona College of Medicine, Tucson, 85724, USA.
Carlo
C
Valentino
Samantha
S
Kendrick
Nathalie
N
Johnson
Randy
R
Gascoyne
Wing C
WC
Chan
Dennis
D
Weisenburger
Rita
R
Braziel
James R
JR
Cook
Raymond
R
Tubbs
Elias
E
Campo
Andreas
A
Rosenwald
German
G
Ott
Jan
J
Delabie
Elaine
E
Jaffe
Wenjun
W
Zhang
Patrick
P
Brunhoeber
Hiro
H
Nitta
Tom
T
Grogan
Lisa
L
Rimsza
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003124:Colorimetry; D003520:Cyclophosphamide / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000032:analysis; D004317:Doxorubicin / Q000627:therapeutic use; D018628:Gene Dosage; D016259:Genes, myc; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005810:Multigene Family; D011241:Prednisone / Q000627:therapeutic use; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014178:Translocation, Genetic; D014750:Vincristine / Q000627:therapeutic use
D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone