Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology

Andersen, Erica; Paxton, Christian N.; O’Malley, Dennis P.; Louissaint, Abner; Hornick, Jason L.; Griffin, Gabriel K.; Fedoriw, Yuri; Kim, Young S.; Weiss, Lawrence M.; Perkins, Sherrie L.; South, Sarah T.

doi:10.1038/modpathol.2017.34

Cited by 30 publications

(25 citation statements)

References 27 publications

(51 reference statements)

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“…Genomic DNA was processed for molecular inversion probe array analysis using the OncoScan FFPE Assay kit (ThermoFisher, Santa Clara, CA, USA), as described (Paxton et al, 2015). Data analysis was performed using Chromosome Analysis software (ChAS) version 3.1 (ThermoFisher) and Nexus Express Software for OncoScan version 3.1 (Biodiscovery, Hawthorne, CA, USA) with reference to assembly GRCh37/hg19, as described (Andersen et al, 2017). All cases were processed using the TuScan segmentation algorithm except for case MG88, which was re-centered and processed using SNP-FASST2.…”

Section: Methodsmentioning

confidence: 99%

Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B-Cell Lymphoma, Leg Type

Zhou

Louissaint

Wenzel

et al. 2018

Journal of Investigative Dermatology

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Cutaneous diffuse large B-cell lymphomas (DLBCLs) are aggressive lymphomas with a poor prognosis. To elucidate their genetic bases, we analyzed exome sequencing of 37 cutaneous DLBCLs, including 31 DLBCLs, leg type (DLBCL-LT) and 6 cutaneous DLBCLs-not otherwise specified (DLBCL-NOS). As reported previously, 77% of DLBCL-LT harbor NF-κB-activating MYD88 mutations. In nearly all MYD88-wild-type DLBCL-LT, we found cancer-promoting mutations that either activate the NF-κB pathway through alternative genes (NFKBIE or REL) or activate other canonical cancer pathways (BRAF, MED12, PIK3R1, and STAT3). After NF-κB, the second most commonly mutated pathway putatively enables immune evasion via mutations predicted to downregulate antigen processing (B2M, CIITA, HLA) or T-cell co-stimulation (CD58). DLBCL-LT have little genetic overlap with the genetically heterogeneous DLBCL-NOS. Instead, they resemble primary central nervous system and testicular large B-cell lymphomas (primary central nervous system lymphomas and primary testicular lymphomas). Like primary central nervous system lymphomas/primary testicular lymphomas, 40% of DLBCL-LT (vs. 0% of DLBCLs-not otherwise specified) harbored PDL1/PDL2 translocations, which lead to overexpression of PD-L1 or PD-L2 in 50% of the cases. Collectively, these data broaden our understanding of cutaneous DLBCLs and suggest novel therapeutic approaches (e.g., BRAF or PI3K inhibitors). Additionally, they suggest novel treatment paradigms, wherein DLBCL-LT can be targeted with strategies (e.g., immune checkpoint blockers) currently being developed for genomically similar primary central nervous system lymphomas/primary testicular lymphomas.

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Section: Methodsmentioning

confidence: 99%

Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B-Cell Lymphoma, Leg Type

Zhou

Louissaint

Wenzel

et al. 2018

Journal of Investigative Dermatology

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“…28 Data analysis was performed with Chromosome Analysis software (ChAS), version 3.2 (Thermo Fisher), and Nexus Express Software for OncoScan, version 3.1 (BioDiscovery, Hawthorne, CA), with reference to assembly GRCh37/hg19, by a published method. 29 All cases were processed with the TuScan segmentation algorithm (ChAS; Thermo Fisher), except for case PS02, which was recentered and processed by using SNP-FASST2 (OncoScan; Nexus Express). Recurrent genomic alterations were calculated with the aggregate analysis in Nexus Express.…”

Section: Copy Number Aberrationsmentioning

confidence: 99%

Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features

et al. 2021

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Primary cutaneous follicle center lymphomas (PCFCLs) are indolent B-cell lymphomas that predominantly remain skin restricted and manageable with skin-directed therapy. Conversely, secondary cutaneous involvement by usual systemic follicular lymphoma (secondary cutaneous follicular lymphoma [SCFL]) has a worse prognosis and often necessitates systemic therapy. Unfortunately, no histopathologic or genetic features reliably differentiate PCFCL from SCFL at diagnosis. Imaging may miss low-burden internal disease in some cases of SCFLs, leading to misclassification as PCFCL. Whereas usual systemic FL is well characterized genetically, the genomic landscapes of PCFCL and SCFL are unknown. Herein, we analyzed clinicopathologic and immunophenotypic data from 30 cases of PCFCL and 10 of SCFL and performed whole-exome sequencing on 18 specimens of PCFCL and 6 of SCFL. During a median follow-up of 7 years, 26 (87%) of the PCFCLs remained skin restricted. In the remaining 4 cases, systemic disease developed within 3 years of diagnosis. Although the SCFLs universally expressed BCL2 and had BCL2 rearrangements, 73% of the PCFCLs lacked BCL2 expression, and only 8% of skin-restricted PCFCLs had BCL2 rearrangements. SCFLs showed low proliferation fractions, whereas 75% of PCFCLs had proliferation fractions >30%. Of the SCFLs, 67% had characteristic loss-of-function CREBBP or KMT2D mutations vs none in skin-restricted PCFCL. Both SCFL and skin-restricted PCFCL showed frequent TNFRSF14 loss-of-function mutations and copy number loss at chromosome 1p36. These data together establish PCFCL as a unique entity with biological features distinct from usual systemic FL and SCFL. We propose 3 criteria based on BCL2 rearrangement, chromatin-modifying gene mutations (CREBBP, KMT2D, EZH2, and EP300), and proliferation index to classify cutaneous FL specimens based on the likelihood of concurrent or future systemic spread.

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“…A tumor suppressor‐driven biology has also been suggested in FDCS. Andersen et al studied genomic alterations of 14 FDCS and found that the majority (11) showed hemizygous deletions affecting multiple chromosomes and involving tumor suppressor genes DKN2A, RB1, BIRC3, and CYLD 26 …”

Section: Discussionmentioning

confidence: 99%

Follicular dendritic cell sarcoma: Cytomorphologic features and diagnostic challenges

Asiry

Khader

Villanueva-Siles

et al. 2021

Diagnostic Cytopathology

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Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm, which primarily arises in lymph nodes with occasional cases occurring in extranodal locations. The diagnosis is often challenging particularly on cytology fine needle aspiration due to overlapping morphologic and immunohistochemical features. We present a case of FDCS diagnosed in an otherwise asymptomatic 33‐year old male. The aim of our case report is to highlight the key cytomorphologic features and discuss various differential diagnoses of this unusual entity.

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Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology

Cited by 30 publications

References 27 publications

Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B-Cell Lymphoma, Leg Type

Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B-Cell Lymphoma, Leg Type

Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features

Follicular dendritic cell sarcoma: Cytomorphologic features and diagnostic challenges

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