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

Publication ,  Journal Article
Xian, RR; Xie, Y; Haley, LM; Yonescu, R; Pallavajjala, A; Pittaluga, S; Jaffe, ES; Duffield, AS; McCall, CM; Gheith, SMF; Gocke, CD
Published in: Blood Cancer J
June 17, 2020

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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Published In

Blood Cancer J

DOI

EISSN

2044-5385

Publication Date

June 17, 2020

Volume

10

Issue

6

Start / End Page

69

Location

United States

Related Subject Headings

  • Translocation, Genetic
  • STAT6 Transcription Factor
  • Polymorphism, Single Nucleotide
  • Mutation
  • Middle Aged
  • Male
  • Lymphoma, Follicular
  • Humans
  • Female
  • Chromosomes, Human, Pair 16
 

Citation

APA
Chicago
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MLA
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Xian, R. R., Xie, Y., Haley, L. M., Yonescu, R., Pallavajjala, A., Pittaluga, S., … Gocke, C. D. (2020). CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma. Blood Cancer J, 10(6), 69. https://doi.org/10.1038/s41408-020-0335-0
Xian, Rena R., Yi Xie, Lisa M. Haley, Raluca Yonescu, Aparna Pallavajjala, Stefania Pittaluga, Elaine S. Jaffe, et al. “CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.Blood Cancer J 10, no. 6 (June 17, 2020): 69. https://doi.org/10.1038/s41408-020-0335-0.
Xian RR, Xie Y, Haley LM, Yonescu R, Pallavajjala A, Pittaluga S, et al. CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma. Blood Cancer J. 2020 Jun 17;10(6):69.
Xian, Rena R., et al. “CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.Blood Cancer J, vol. 10, no. 6, June 2020, p. 69. Pubmed, doi:10.1038/s41408-020-0335-0.
Xian RR, Xie Y, Haley LM, Yonescu R, Pallavajjala A, Pittaluga S, Jaffe ES, Duffield AS, McCall CM, Gheith SMF, Gocke CD. CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma. Blood Cancer J. 2020 Jun 17;10(6):69.

Published In

Blood Cancer J

DOI

EISSN

2044-5385

Publication Date

June 17, 2020

Volume

10

Issue

6

Start / End Page

69

Location

United States

Related Subject Headings

  • Translocation, Genetic
  • STAT6 Transcription Factor
  • Polymorphism, Single Nucleotide
  • Mutation
  • Middle Aged
  • Male
  • Lymphoma, Follicular
  • Humans
  • Female
  • Chromosomes, Human, Pair 16