Deletions in metastatic colorectal cancer with chromothripsis

Skuja, Elīna; Butane, Dagnija; Nakazawa-Miklaševiča, Miki; Daneberga, Zanda; Purkalne, Gunta; Miklaševičs, Edvīns

doi:10.32471/exp-oncology.2312-8852.vol-41-no-4.13841

Cited by 12 publications

(9 citation statements)

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“…One of the rst steps in the cellular response to DNA damage induced by exogenous agents is DNA repair protein activation [35][36][37]. The literature suggests that CNVs may be important genetic variants that explain tumor heterogeneity and genetic instability in CRC [38][39][40]. Therefore, we suggest that these CNVs are initialization markers of cellular abnormality.…”

Section: Discussionmentioning

confidence: 88%

Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

Rocha¹,

Zanardo²,

Dias³

et al. 2021

Preprint

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The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in patients with sporadic colorectal cancer (CRC) using multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism arrays. The results revealed pathogenic genomic alterations in the TNFRS18 (1p), CHL1 (3p), TRIML2 (4q), FBXO25 (8p), NKX3-1 (8p), RECQL4 (8q), DOCK8 (9p), ZMYND11 (10p), KDM5A (12p), PSPC1 (13q), ADPRTL2 (14q), MTA1 (14q), DECR2 (16p), GAS8 (16q), THOC1 (18p), CTDP1 (18q), SOX12 (20p), ADRM1 (20q), UCKL1 (20q), OPRL1 (20q), IL17RA (22q), and SYBL1 (Xq) genes. We detected copy number variations (CNVs) with frequencies greater than 40% in the probes located in 20q, which contains very important genes in the study of tumors. These findings showed instability in the tumor genome and altered regions associated with cell migration, transcription activation, apoptosis, and immune system deregulation. Unexpectedly, we detected concomitant pathogenic CNVs in tumors and surrounding tissues. Our data suggest that characterizing the genomic CRC profile is an important contribution to better understanding instability as a mechanism of carcinogenesis in CRC patients.

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Section: Discussionmentioning

confidence: 88%

Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

Rocha¹,

Zanardo²,

Dias³

et al. 2021

Preprint

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“…The functions and mechanisms of ROBO2 in tumor progression are gradually being recognized. Skuja et al found that ROBO2 deletion was identi ed in more than half of patients with metastatic colorectal cancer [20]. However, through L1-targeted resequencing of colorectal tumors and matched normal DNA, Solyom et al described ROBO2 as an oncogene [21].…”

Section: Discussionmentioning

confidence: 99%

Robo2 Predicts a Better Prognosis and Inhibits Malignant Behavior in Vivo in Pancreatic Ductal Adenocarcinoma

Ding

Wang

et al. 2021

Preprint

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BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with an extremely poor prognosis and a high mortality rate. Genome-wide studies have shown that the SLIT/ROBO signaling pathway plays an important role in pancreatic tumor development and progression. However, the effect and mechanism of ROBO2 in the progression of pancreatic cancer remains largely unknown.MethodsIn this study, real-time polymerase chain reaction (RT-PCR) and western blot analyses were adopted to evaluate the expression level of ROBO2 and proteins in pancreatic cell lines. Cell migration and invasion and cell proliferation were conducted in AsPC-1 and MIA PaCa-2 cell lines. RNA sequencing and western blot were undertaken to explore the mechanisms and potential targeted molecules. ROBO2 expression in tumor tissues was evaluated by immunohistochemistry in 95 patients.ResultsROBO2 expression was downregulated in PDAC cell lines and tissue samples. A high level of ROBO2 was associated with good overall survival. Upregulation of ROBO2 inhibited PDAC cell proliferation, migration, and invasion, whereas the opposite results were found in the ROBO2 downregulation group. In addition, xenograft animal models further confirmed the effect of ROBO2 on proliferation. Finally, the RNA sequencing results indicated that ROBO2 facilitates anti-tumorigenicity partly via inhibiting ECM1 in PDAC. ConclusionsOur work suggests that ROBO2 inhibits tumor progression in PDAC and may serve as a predictive biomarker and therapeutic target in PDAC.

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“…Bioinformatics analysis. Quantile normalization and low-intensity filtering were performed using R software package (R Version 3.1.2) (18). Next, the circRNAs detected in >50% samples were subjected to further analysis.…”

Section: Methodsmentioning

confidence: 99%

Dysregulated circular RNAs are closely linked to multiple myeloma prognosis, with circ_0026652 predicting bortezomib‑based treatment response and survival via the microRNA‑608‑mediated Wnt/β‑catenin pathway

Liu

et al. 2022

Oncol Rep

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Circular RNA (circRNA/circ) profiles have been suggested to be involved in the prognosis of several types of solid tumors and hematological malignancies, including multiple myeloma (MM). Therefore, the aim of the present study was to comprehensively explore the involvement of circRNA profiles in MM prognosis. A total of 60 patients with MM that underwent bortezomib-based induction therapy were enrolled. Next, eight patients with complete response (CR) and eight with no response (NR) were randomly selected to detect their circRNA profiles in bone marrow plasma cells (BMPCs) by microarray. Next, 10 candidate circRNAs were verified via reverse transcription-quantitative PCR (RT-qPCR) in the BMPCs of 60 patients with MM. Finally, the molecular mechanism of circ_0026652 knockdown underlying the regulation of chemosensitivity to bortezomib was assessed. Microarray showed that 79 circRNAs were upregulated and 167 were downregulated in CR compared with NR cases, which were found to be enriched in carcinogenic and chemoresistance-related pathways (Wnt, mTOR and MAPK pathways). RT-qPCR showed that 8/10 circRNAs (circ_0026652, circ_0068708, circ_0088128, circ_0001566, circ_0031113, circ_0083587, circ_0005552 and circ_0007171) were associated with treatment response [CR or objective response rate (ORR)] and 5/10 circRNAs (circ_0026652, circ_0068708, circ_0001566, circ_0031113 and circ_0005552) were associated with progression-free survival (PFS) or overall survival (OS). Of note, circ_0026652 was a key prognostic marker simultaneously associated with CR, ORR, PFS and OS. Cellular experiments showed that circ_0026652 knockdown enhanced chemosensitivity to bortezomib through the microRNA (miR)-608-mediated Wnt/β-catenin pathway in U266 and RPIM-8226 cells. In conclusion, dysregulated circRNA profiles were closely associated with MM prognosis, with circ_0026652 being linked to bortezomib-based treatment response and survival through the miR-608-mediated Wnt/β-catenin pathway.

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Deletions in metastatic colorectal cancer with chromothripsis

Cited by 12 publications

References 0 publications

Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

Robo2 Predicts a Better Prognosis and Inhibits Malignant Behavior in Vivo in Pancreatic Ductal Adenocarcinoma

Dysregulated circular RNAs are closely linked to multiple myeloma prognosis, with circ_0026652 predicting bortezomib‑based treatment response and survival via the microRNA‑608‑mediated Wnt/β‑catenin pathway

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