Genes & Genomics

, Volume 40, Issue 12, pp 1279–1285 | Cite as

A case of interdigitating dendritic cell sarcoma studied by whole-exome sequencing

  • Ki Hwan Hong
  • Soyoung Song
  • Wonseok Shin
  • Keunsoo Kang
  • Chun-Sung Cho
  • Yong Tae Hong
  • Kyudong HanEmail author
  • Jeong Hwan MoonEmail author
Research Article


Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm and is an extremely rare disease, with a challenging diagnosis. Etiology of IDCS is also unknown and most studies with only case reports. In our case, immunohistochemistry showed that the tumor cells were positive for S100, CD45, and CD68, but negative for CD1a and CD21. This study aimed to investigate the causative factors of IDCS by sequencing the protein-coding regions of IDCS. We performed whole-exome sequencing with genomic DNA from blood and sarcoma tissue of the IDCS patient using the Illumina Hiseq 2500 platform. After that, we conducted Sanger sequencing for validation of sarcoma-specific variants and gene ontology analysis using DAVID bioinformatics resources. Through comparing sequencing data of sarcoma with normal blood, we obtained 15 nonsynonymous single nucleotide polymorphisms (SNPs) as sarcoma-specific variants. Although the 15 SNPs were not validated by Sanger sequencing due to tumor heterogeneity and low sensitivity of Sanger sequencing, we examined the function of the genes in which each SNP is located. Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the IDCS. Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis.


Interdigitating dendritic cell sarcoma Whole-exome sequencing POLQ FNIP1 



This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1C1B5017565).

Compliance with ethical standards

Conflict of interest

Ki Hwan Hong, Soyoung Song, Wonseok Shin, Keunsoo Kang, Chun-Sung Cho, Yong Tae Hong, Kyudong Han, and Jeong Hwan Moon declare that we have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.

Supplementary material

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  1. Altimari A et al (2013) 454 next generation-sequencing outperforms allele-specific PCR, Sanger sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin-fixed, paraffin-embedded samples. OncoTargets Ther 6:1057–1064. CrossRefGoogle Scholar
  2. Barwell N, Howatson R, Jackson R, Johnson A, Jarrett RF, Cook G (2004) Interdigitating dendritic cell sarcoma of salivary gland associated lymphoid tissue not associated with HHV-8 or EBV infection. J Clin Pathol 57:87–89CrossRefGoogle Scholar
  3. Brandalize AP, Schuler-Faccini L, Hoffmann JS, Caleffi M, Cazaux C, Ashton-Prolla P (2014) A DNA repair variant in POLQ (c.-1060A> G) is associated to hereditary breast cancer patients: a case-control study. BMC Cancer 14:850. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Guo G et al (2013) Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet 45:1459–1463. CrossRefGoogle Scholar
  5. Hasumi H et al (2015) Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn. Proc Natl Acad Sci USA 112:E1624–E1631. CrossRefPubMedGoogle Scholar
  6. Higgins GS, Harris AL, Prevo R, Helleday T, McKenna WG, Buffa FM (2010) Overexpression of POLQ confers a poor prognosis in early breast cancer patients. Oncotarget 1:175–184. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Johnson RL, Boisot S, Ball ED, Wang HY (2014) A case of interdigitating dendritic cell sarcoma/histiocytic sarcoma–a diagnostic pitfall. Int J Clin Exp Pathol 7:378–385PubMedGoogle Scholar
  8. Kawamura K et al (2004) DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers. Int J Cancer 109:9–16. CrossRefPubMedGoogle Scholar
  9. Khoo SK et al (2002) Clinical and genetic studies of Birt-Hogg-Dube syndrome. J Med Genet 39:906–912CrossRefGoogle Scholar
  10. Kim SY et al (2010) Interdigitating dendritic cell sarcoma of the tonsil. Asia-Pac J Clin Oncol 6:144–148. CrossRefPubMedGoogle Scholar
  11. Kim S et al (2017) Strelka2: fast and accurate variant calling for clinical sequencing applications. bioRxiv CrossRefGoogle Scholar
  12. Lemee F et al (2010) DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability. Proc Natl Acad Sci USA 107:13390–13395. CrossRefPubMedGoogle Scholar
  13. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Liang H et al (2012) Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. Genome Res 22:2120–2129. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Magro CM, Olson LC, Nuovo G, Solomon GJ (2017) Primary cutaneous interdigitating dendritic cell sarcoma is a morphologic and phenotypic simulator of poorly differentiated metastatic melanoma: a report of 2 cases and review of the literature. Ann Diagn Pathol 30:59–65. CrossRefPubMedGoogle Scholar
  16. Orii T, Takeda H, Kawata S, Maeda K, Yamakawa M (2010) Differential immunophenotypic analysis of dendritic cell tumours. J Clin Pathol 63:497–503. CrossRefPubMedGoogle Scholar
  17. Pillaire MJ et al (2010) A ‘DNA replication’ signature of progression and negative outcome in colorectal cancer. Oncogene 29:876–887. CrossRefPubMedGoogle Scholar
  18. Pokuri VK, Merzianu M, Gandhi S, Baqai J, Loree TR, Bhat S (2015) Interdigitating dendritic cell sarcoma. J Natl Compr Cancer Netw 13:128–132CrossRefGoogle Scholar
  19. Rosenberg SA, Niglio SA, Jo VY, Goydos JS (2014) Interdigitating dendritic cell sarcoma presenting in the skin: diagnosis and the role of surgical resection, chemotherapy and radiotherapy in management. Rare Tumors 6:5573. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Saunders CT, Wong WS, Swamy S, Becq J, Murray LJ, Cheetham RK (2012) Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28:1811–1817. CrossRefPubMedGoogle Scholar
  21. Tarasov A, Vilella AJ, Cuppen E, Nijman IJ, Prins P (2015) Sambamba: fast processing of NGS alignment formats. Bioinformatics 31:2032–2034. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Wang K, Li MY, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164CrossRefGoogle Scholar
  23. Witkiewicz AK et al (2015) Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun 6:6744. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Xue T, Jiang XN, Wang WG, Zhou XY, Li XQ (2018) Interdigitating dendritic cell sarcoma: clinicopathologic study of 8 cases with review of the literature. Ann Diagn Pathol 34:155–160. CrossRefPubMedGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Otolaryngology-Head and Neck SurgeryChonbuk National University Medical SchoolJeonjuRepublic of Korea
  2. 2.Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative MedicineDankook UniversityCheonanRepublic of Korea
  3. 3.Department of MicrobiologyDankook UniversityCheonanRepublic of Korea
  4. 4.Department of Neurosurgery, College of MedicineDankook UniversityCheonanRepublic of Korea
  5. 5.Department of Otorhinolaryngology-Head and Neck Surgery, College of MedicineDankook UniversityCheonanRepublic of Korea

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