CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.

Szczegóły
Abstrakt

Tytuł:: CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.
Autorzy:: Xian RR; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.; Pathology and Lab Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Xie Y; Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.; Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Haley LM; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Yonescu R; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Pallavajjala A; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Pittaluga S; Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Jaffe ES; Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Duffield AS; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
McCall CM; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
Gheith SMF; Pathology and Laboratory Medicine, Lehigh Valley Health Network, Allentown, PA, USA.
Gocke CD; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. .; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. .
Źródło:: Blood cancer journal [Blood Cancer J] 2020 Jun 17; Vol. 10 (6), pp. 69. Date of Electronic Publication: 2020 Jun 17.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
Język:: English
Imprint Name(s):: Original Publication: New York, NY : Nature Pub. Group
MeSH Terms:: CREB-Binding Protein/*genetics
Lymphoma, Follicular/*genetics
STAT6 Transcription Factor/*genetics
Adult ; Aged ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 16 ; Female ; Humans ; Lymphoma, Follicular/pathology ; Male ; Middle Aged ; Mutation ; Polymorphism, Single Nucleotide ; Translocation, Genetic
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Grant Information:: P30 CA006973 United States CA NCI NIH HHS
Substance Nomenclature:: 0 (STAT6 Transcription Factor)
0 (STAT6 protein, human)
EC 2.3.1.48 (CREB-Binding Protein)
EC 2.3.1.48 (CREBBP protein, human)
Entry Date(s):: Date Created: 20200620 Date Completed: 20210510 Latest Revision: 20210617
Update Code:: 20240105
PubMed Central ID:: PMC7299932
DOI:: 10.1038/s41408-020-0335-0
PMID:: 32555149
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The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic review, FISH, SNP-microarray, and next-generation sequencing of 16 cases of dFL. We found unique morphologic features, including interstitial sclerosis, microfollicle formation, and rounded nuclear cytology, confirmed absence of t(14;18) and recurrent deletion of 1p36, and showed a novel association with deletion/CN-LOH of 16p13 (inclusive of CREBBP, CIITA, and SOCS1). Mutational profiling demonstrated near-uniform mutations in CREBBP and STAT6, with clonal dominance of CREBBP, among other mutations typical of germinal-center B-cell lymphomas. Frequent CREBBP and CIITA codeletion/mutation suggested a mechanism for immune evasion, while subclonal STAT6 activating mutations with concurrent SOCS1 loss suggested a mechanism of BCL-xL/BCL2L1 upregulation in the absence of BCL2 rearrangements. A review of the literature showed significant enrichment for 16p13 and 1p36 loss/CN-LOH, STAT6 mutation, and CREBBP and STAT6 comutation in dFL, as compared with conventional FL. With this comprehensive approach, our study demonstrates confirmatory and novel genetic associations that can aid in the diagnosis and subclassification of this rare type of lymphoma.

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