Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer

Yu, Jian; Wu, William Ka Kei; Liang, Qiaoyi; Zhang, N; He, Jun; Li, X; Zhang, X; Lin, Xu; Chan, Matthew T. V.; Ng, Simon Siu Man; Sung, Joseph J.Y.

doi:10.1038/onc.2015.72

Cited by 28 publications

(24 citation statements)

References 42 publications

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“…Chromatin remodeling is one of the most frequently inactivated biological processes in SCC, and has been demonstrated to be involved in either tumor initiation or progression in multiple cancer types (Andricovich et al, 2018;Cho et al, 2018;Dhar et al, 2018;Jia et al, 2018;Mathur et al, 2017;Yu et al, 2016). In our SB cuSCC screen, chromatin remodeling was the top biological process that was significantly enriched ( Supplementary Table 28).…”

Section: Chromatin Modifying Tumor Suppressors Drive Human Keratinocymentioning

confidence: 94%

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression

Aiderus

Newberg

Guzman-Rojas

et al. 2019

Preprint

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30The systematic identification of genetic events driving cellular transformation and tumor progression in the absence 31 of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell 32 carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular 33 landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically 34 define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified 35 established tumor suppressor genes, as well as previously unknown oncogenic drivers of cuSCC. Functional analysis 36 confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the 37 initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely 38 heterogeneous genetic landscape of cuSCC initiation and progression, which could be harnessed to better 39 understand skin oncogenic etiology and prioritize therapeutic candidates. 40

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Section: Chromatin Modifying Tumor Suppressors Drive Human Keratinocymentioning

confidence: 94%

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression

Aiderus

Newberg

Guzman-Rojas

et al. 2019

Preprint

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“…7 Translocations involving NCOA2 have been observed in mesenchymal chondrosarcoma, spindle cell rhabdomyosarcoma, prostate cancer, colon cancer, acute leukemia, and soft tissue angiofibroma, whereas ETV3 abnormalities have been For [6][7][8][9] Neoplastic associations of ICH are limited to case reports that include patients with mast cell leukemia, acute myeloid leukemia, and B-cell lymphoma.…”

mentioning

confidence: 99%

ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis

Brown

Kwong

McCalmont

et al. 2015

Blood

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Indeterminate cell histiocytosis (ICH) is a rare and controversial disorder first described by Wood et al 1 in 1985. ICH is characterized by a nonepidermotropic histiocytic infiltrate with immunohistochemical features that overlap with Langerhans cells (LCs) and nonLCs of monocyte-macrophage-dendritic cell lineage.1 It is unclear whether ICH is distinct from Langerhans cell histiocytosis (LCH) or instead represents a variant form of LCH. The gold standard for distinguishing ICH from LCH is demonstration of the absence of Birbeck granules by electron microscopy or, more practically, through use of langerin (CD207) immunohistochemistry (IHC), which is positive in LCH and non-reactive in ICH.2 Although LCH is understood to be a clonal proliferation, there has not been sufficient support for a common molecular pathway in ICH in the literature to date, leading some authors to consider ICH a reactive condition. Herein, we present 3 cases of ICH with a recurrent ETV3-NCOA2 translocation. This molecular finding provides evidence that ICH is a true clonal entity deserving of separate classification.Patient 1 was a 62-year-old woman who presented with a 30-year history of innumerable dome-shaped smooth red and brown papules and nodules scattered diffusely over her face, chest, back, and extremities. Skin biopsy demonstrated a dermal infiltrate of mononuclear histiocytes highlighted by CD1a and CD68 without langerin reactivity. Scattered mature lymphocytes and rare eosinophils were intermixed. S100 was positive in 5% of the histiocytic infiltrate. Electron microscopy confirmed the absence of Birbeck granules. Targeted next-generation sequencing was performed by Foundation Medicine (Cambridge, MA) using the previously described FoundationOne assay, 3 and it revealed an ETV3-NCOA2 gene fusion characterized as 59-ETV3(x1-4)1 NCOA2(x14-23)-39 resulting in an aberrant NCOA2. Other aberrant mutations, including those involving the RAS-RAF-MEK pathway, were not found. BRAF V600E IHC was negative. Fluorescence in situ hybridization (FISH) for the ETV3-NCOA2 translocation was positive (Figure 1, inset).Patient 2 was a 51-year-old woman who presented with a severalweek history of diffuse nonpruritic papules involving her arms, legs, neck, scalp, face, chest, and back. Histopathologic examination of a skin biopsy demonstrated a dermal infiltrate composed of mononuclear histiocytes with eosinophilic cytoplasm and admixed mature-appearing lymphocytes. The histiocytes were positive for S100, CD68, and CD1a, whereas langerin and BRAF V600E IHC were negative. FISH testing for the ETV3-NCOA2 translocation was positive (Figure 1).Patient 3 was an 81-year-old man who presented with a solitary lesion on the upper arm which had been present for approximately 6 months. Biopsy showed a multinodular dermal infiltrate of large, oval cells with abundant pale eosinophilic cytoplasm and reniform nuclei. The lesional cells were positive for S100, CD68, and CD1a, whereas langerin and BRAF V600E IHC were negative. FISH testing for the ETV3-NCOA2 translo...

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“…Studies on genomic rearrangements in CRC have led to discovering VTI1A-TCF7L2 and R-spondin fusions (PTPRK-RSPO3 and EIF3E-RSPO2) as essential gene fusions [ 14 , 15 , 16 , 17 ]. Since then, other fusion transcripts with different prevalence rates have been documented in CRC [ 15 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

Panza

Castellana

Biscaglia

et al. 2020

IJMS

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Fusion genes and epigenetic regulators (i.e., miRNAs and long non-coding RNAs) constitute essential pieces of the puzzle of the tumor genomic landscape, in particular in mechanisms behind the adenoma-to-carcinoma progression of colorectal cancer (CRC). In this work, we aimed to identify molecular signatures of the different steps of sporadic CRC development in eleven patients, of which synchronous samples of adenomas, tumors, and normal tissues were analyzed by RNA-Seq. At a functional level, tumors and adenomas were all characterized by increased activity of the cell cycle, cell development, cell growth, and biological proliferation functions. In contrast, organic survival and apoptosis-related functions were inhibited both in tumors and adenomas at different levels. At a molecular level, we found that three individuals shared a tumor-specific fusion named MRPS31-SUGT1, generated through an intra-chromosomal translocation on chromosome 13, whose sequence resulted in being 100% identical to the long non-coding RNA (lncRNA) MRPS31P5. Our analyses suggest that MRPS31P5 could take part to a competitive endogenous (ce)RNA network by acting as a miRNA sponge or/and as an interactor of other mRNAs, and thus it may be an important gene expression regulatory factor and could be used as a potential biomarker for the detection of early CRC events.

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Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer

Cited by 28 publications

References 42 publications

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression

ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis

Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

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