Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone.

Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi

Research output: Contribution to journalArticle

Abstract

Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas. Sixteen cases of non-metastatic GCTB, 9 GCTB with lung metastases, and 35 giant cell-rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using conventional polymerase chain reaction (PCR) and fast COamplification at Lower Denaturation temperature-PCR (COLD-PCR). Overall, 24 GCTB (96%) presented a mutation in the H3F3A gene (15 of 16 non metastatic and 9 of 9 metastatic). Five sarcomas harbored a H3F3A mutation (3 p.G35 W, 1 p.G35 L and 1 p.G35E), and these were all secondary malignant GCTB. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cell rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered
Original languageEnglish
Pages (from-to)128-135
Number of pages8
JournalHuman Pathology
Volume68
DOIs
Publication statusPublished - Sep 2017

Fingerprint

Giant Cell Tumor of Bone
Giant Cell Tumors
Giant Cells
Sarcoma
Histones
Bone and Bones
Mutation
Chondroblastoma
Codon
Genes
Polymerase Chain Reaction
Paraffin
Formaldehyde
Differential Diagnosis
Neoplasm Metastasis

Keywords

  • COLD-PCR
  • Giant cell rich sarcomas
  • Giant cell tumor of bone
  • Histone 3.3 gene mutations
  • Malignant giant cell tumor

Cite this

Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone. / Righi, Alberto; Mancini, Irene; Gambarotti, Marco; Picci, Piero; Gamberi, Gabriella; Marraccini, Cristina; Tos, Angelo Paolo Dei; Simi, Lisa; Pinzani, Pamela; Franchi, Alessandro.

In: Human Pathology, Vol. 68, 09.2017, p. 128-135.

Research output: Contribution to journalArticle

Righi, A, Mancini, I, Gambarotti, M, Picci, P, Gamberi, G, Marraccini, C, Tos, APD, Simi, L, Pinzani, P & Franchi, A 2017, 'Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone.', Human Pathology, vol. 68, pp. 128-135. https://doi.org/0.1016/j.humpath.2017.08.033
Righi, Alberto ; Mancini, Irene ; Gambarotti, Marco ; Picci, Piero ; Gamberi, Gabriella ; Marraccini, Cristina ; Tos, Angelo Paolo Dei ; Simi, Lisa ; Pinzani, Pamela ; Franchi, Alessandro. / Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone. In: Human Pathology. 2017 ; Vol. 68. pp. 128-135.
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