Identification of a novel, recurrent MBTD1‐CXorf67 fusion in low‐grade endometrial stromal sarcoma. Issue 5 (4th September 2013)

• Record Type: Journal Article
• Authors: Dewaele, Barbara; Przybyl, Joanna; Quattrone, Anna; Finalet Ferreiro, Julio; Vanspauwen, Vanessa; Geerdens, Ellen; Gianfelici, Valentina; Kalender, Zeynep; Wozniak, Agnieszka; Moerman, Philippe; Sciot, Raf; Croce, Sabrina; Amant, Frederic; Vandenberghe, Peter; Cools, Jan; Debiec‐Rychter, Maria
• Is Part Of: International journal of cancer. Volume 134:Issue 5(2014:Mar. 01)
• Page Start: 1112
• Page End: 1122
• Publication Date: 2013-09-04
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28440
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are commonly driven by recurrent gene rearrangements. In conventional low‐grade ESS, <italic>JAZF1‐SUZ12</italic>, <italic>PHF1‐JAZF1</italic>, <italic>EPC1‐PHF1</italic> and <italic>MEAF6‐PHF1</italic>, and recently described <italic>ZC3H7</italic>‐<italic>BCOR</italic> chimeric fusions have been reported in > 50% of cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE‐FAM22A/B chimeric proteins that are associated with histologically high‐grade and clinically more aggressive ESS. Integrating whole‐transcriptome paired‐end RNA sequencing with fluorescence <italic>in situ</italic> hybridization (FISH) and banding cytogenetics, we identified <italic>MBTD1</italic> (malignant brain tumor domain‐containing 1) and <italic>CXorf67</italic> (chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low‐grade ESS of classical histology. The presence of the <italic>MBTD1‐CXorf67</italic> fusion transcript was validated in both cases using reverse‐transcription polymerase chain reaction followed by Sanger sequencing. A specific FISH assay was developed to detect the novel t(X;17) translocation in formalin‐fixed paraffin‐embedded material, and resulted in identification of an additional low‐grade ESS case positive for the <italic>MBTD1‐CXorf67</italic> fusion among 25 uterine stromal tumors [14 ESS and 11 undifferentiated endometrial sarcomas (UESs)] that were negative for <italic>JAZF1</italic> and <italic>YWHAE</italic> rearrangements. Gene expression profiles of seven ESS (including three with <italic>YWHAE</italic> and two with <italic>JAZF1</italic> rearrangements) and four UES without specific chromosomal aberrations indicated clustering of tumors with <italic>MBTD1‐CXorf67</italic> fusion together with low‐grade <italic>JAZF1</italic>‐associated ESS. The chimeric <italic>MBTD1‐CXorf67</italic> fusion identifies yet another cytogenetically distinct subgroup of low‐grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes.</p> </abstract>