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RNA-sequencing identifies novel GREB1-NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13).

ABSTRACT: Sarcomas account for 3% of all uterine malignancies and many of them are characterized by acquired, specific fusion genes whose detection has increased pathogenetic knowledge and diagnostic precision. We describe a novel fusion gene, GREB1-NCOA2, detected by transcriptome sequencing and validated by reverse transcriptase polymerase chain reaction and Sanger sequencing in an undifferentiated uterine sarcoma. The chimeric transcript was an in-frame fusion between exon 3 of GREB1 and exon 15 of NCOA2. The fusion is reported here for the first time, but it involves the GREB1 gene, an important promoter of tumor growth and progression, and NCOA2 which is known to be involved in transcriptional regulation. The alteration and recombination of these genes played a role in the tumorigenesis and/or progression of this sarcoma.

SUBMITTER: Brunetti M

PROVIDER: S-EPMC5838407 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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RNA-sequencing identifies novel GREB1-NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13).

Brunetti Marta M Panagopoulos Ioannis I Gorunova Ludmila L Davidson Ben B Heim Sverre S Micci Francesca F

Genes, chromosomes & cancer 20171221 4

Sarcomas account for 3% of all uterine malignancies and many of them are characterized by acquired, specific fusion genes whose detection has increased pathogenetic knowledge and diagnostic precision. We describe a novel fusion gene, GREB1-NCOA2, detected by transcriptome sequencing and validated by reverse transcriptase polymerase chain reaction and Sanger sequencing in an undifferentiated uterine sarcoma. The chimeric transcript was an in-frame fusion between exon 3 of GREB1 and exon 15 of NCO ...[more]

PMID: 29218853

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Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

Project description:We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA?sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in?frame TBCK?P4HA2 and the reciprocal but out?of?frame P4HA2?TBCK fusion transcripts. The putative TBCK?P4HA2 protein would contain the kinase, the rhodanese?like domain, and the Tre?2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4?hydroxylase. The t(5;8;17)(p15;q13;q21) three?way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in?frame fusions AHRR?NCOA2 and NCOA2?ETV4 as well as an out?of?frame ETV4?AHRR transcript. In the AHRR?NCOA2 protein, the C?terminal part of AHRR is replaced by the C?terminal part of NCOA2 which contains two activation domains. The NCOA2?ETV4 protein would contain the helix?loop?helix, PAS_9 and PAS_11, CITED domains, the SRC?1 domain of NCOA2 and the ETS DNA?binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR?NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

| S-EPMC5055197 | biostudies-literature

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