Comprehensive genomic profiling of a rare thyroid follicular dendritic cell sarcoma

Jaime I. Davila, Jason S. Starr, Steven Attia, Chen Wang, Ryan A. Knudson, Brian M. Necela, Vivekananda Sarangi, Zhifu D Sun, Yingxue Ren, John D. Casler, David M. Menke, Gavin R. Oliver, Richard W Joseph, John A III Copland, Alexander Parker, Jean-Pierre Kocher, E Aubrey Thompson, Robert Christian Smallridge, Yan Asmann

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We previously reported an extremely rare case of follicular dendritic cell sarcoma (FDCS) presented as a thyroid mass. Given the rarity of this disease, there are no personalized and molecularly targeted treatment options due to the lack of knowledge in the genomic makeup of the tumor. A 44- year-old white woman was diagnosed with an extranodal FDCS in thyroid. The patient underwent a total thyroidectomy, central compartment dissection, parathyroid reimplantation, and adjuvant radiation therapy. Tumor DNA sequencing of 236 genes by FoundationOne panel found truncating mutations in PTEN and missense mutations in RET and TP53. However, patientmatched germline DNA was not sequenced which is critical for identification of true somatic mutations. Furthermore, the FoundationOne panel doesn’t measure genomic rearrangements which have been shown to be abundant in sarcomas and are associated with sarcoma tumorigenesis and progression. In the current study, we carried out comprehensive genomic sequencing of the tumor, adjacent normal tissues, and patient-matched blood, in an effort to understand the genomic makeup of this rare extranodal FDCS and to identify potential therapeutic targets. Eighty-one somatic point mutations were identified in tumor but not in adjacent normal tissues or blood. A clonal truncating mutation in the CLTCL1 gene, which stabilizes the mitotic spindle, was likely a driver mutation of tumorigenesis and could explain the extensive copy number aberrations (CNAs) and genomic rearrangements in the tumor including a chr15/chr17 local chromothripsis resulted in 6 expressed fusion genes. The fusion gene HDGFRP3→SHC4 led to a 200-fold increase in the expression of oncogene SHC4 which is a potential target of the commercial drug Dasatinib. Missense mutations in ATM and splice-site mutation in VEGFR1 were also detected in addition to the TP53 missense mutation reported by FoundationOne.

Original languageEnglish (US)
Article number6834
Pages (from-to)50-53
Number of pages4
JournalRare Tumors
Volume9
Issue number2
DOIs
StatePublished - Sep 15 2017

Fingerprint

Follicular Dendritic Cell Sarcoma
Missense Mutation
Mutation
Gene Fusion
Neoplasms
Sarcoma
Thyroid Gland
Carcinogenesis
Spindle Apparatus
Replantation
Thyroidectomy
DNA Sequence Analysis
Oncogenes
Point Mutation
Genes
Dissection
Radiotherapy
Thyroid Epithelial Cells
DNA
Therapeutics

Keywords

  • Fusion
  • Genomic rearrangement
  • Genomic sequencing
  • Thyroid FDCS

ASJC Scopus subject areas

  • Histology
  • Oncology

Cite this

Comprehensive genomic profiling of a rare thyroid follicular dendritic cell sarcoma. / Davila, Jaime I.; Starr, Jason S.; Attia, Steven; Wang, Chen; Knudson, Ryan A.; Necela, Brian M.; Sarangi, Vivekananda; Sun, Zhifu D; Ren, Yingxue; Casler, John D.; Menke, David M.; Oliver, Gavin R.; Joseph, Richard W; Copland, John A III; Parker, Alexander; Kocher, Jean-Pierre; Thompson, E Aubrey; Smallridge, Robert Christian; Asmann, Yan.

In: Rare Tumors, Vol. 9, No. 2, 6834, 15.09.2017, p. 50-53.

Research output: Contribution to journalArticle

Davila, Jaime I. ; Starr, Jason S. ; Attia, Steven ; Wang, Chen ; Knudson, Ryan A. ; Necela, Brian M. ; Sarangi, Vivekananda ; Sun, Zhifu D ; Ren, Yingxue ; Casler, John D. ; Menke, David M. ; Oliver, Gavin R. ; Joseph, Richard W ; Copland, John A III ; Parker, Alexander ; Kocher, Jean-Pierre ; Thompson, E Aubrey ; Smallridge, Robert Christian ; Asmann, Yan. / Comprehensive genomic profiling of a rare thyroid follicular dendritic cell sarcoma. In: Rare Tumors. 2017 ; Vol. 9, No. 2. pp. 50-53.
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AU - Necela, Brian M.

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