Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy

Carotenuto, Marianeve; Sacco, Alessandra; Forgione, Laura; Normanno, Nicola

doi:10.37349/etat.2022.00079

Cited by 15 publications

(12 citation statements)

References 146 publications

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“…Previous studies showed that am EGFR TKI induced FGFR3 signaling by de-repressing FGFR3 expression, and FGFGR3 signaling is a key signaling pathway in the regulation of EGFR TKI resistance ( 30 - 32 ). Thus, de novo FGFR3 high expression may be significantly related to the EGFR mutation state of activation in treatment-naive NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

Lin¹,

Long²,

Chen³

et al. 2023

J Thorac Dis

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Background This study sought to examine the expression and mutation status of fibroblast growth factor receptor 3 (FGFR3) in non-small cell lung cancer (NSCLC) tissues and explore the prognostic potential of FGFR3 in NSCLC. Methods Immunohistochemistry (IHC) was used to evaluate the FGFR3 protein expression of 116 NSCLC tissues. Sanger sequencing was used to examine the mutation status of exons 7, 10, and 15 in FGFR3. A Kaplan‑Meier survival analysis was conducted to evaluate the association between the expression level of FGFR3 and the overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Univariate and multivariate Cox analyses were conducted to examine the association between the risk score and clinical features. Results FGFR3 was immunoreactive in 26 of the 86 NSCLC cases. Further, FGFR3 was positively expressed in 84.6% of the lung adenocarcinoma (AC) cases and 15.4% of the lung squamous cell carcinoma (SCC) cases. FGFR3 mutations were detected in 2 NSCLC patients (2/72, 2.8%), who both harbored the T450M mutation, a novel mutation in exon 10 of FGFR3. In NSCLC, a high expression of FGFR3 was positively correlated with gender, smoking, histology type, T stage, and the epidermal growth factor receptor (EGFR) mutation (P<0.05). FGFR3 expression was also correlated with better OS and DFS. The multivariate analysis revealed that FGFR3 served as an independent prognostic factor (P=0.024) for the OS of NSCLC patients. Conclusions This study showed that FGFR3 was highly expressed in NSCLC tissues, and the frequency rate for the FGFR3 mutation at T450 M in NSCLC tissues was low. The survival analysis suggested that FGFR3 may be a useful prognostic biomarker in NSCLC.

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Section: Discussionmentioning

confidence: 99%

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

Lin¹,

Long²,

Chen³

et al. 2023

J Thorac Dis

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“…Subsequently, additional drugs targeting FGFR2 gene fusion/rearrangement received regulatory approvals as second-line or subsequent treatments for advanced CCA [ 109 , 110 ]. Recent approvals of tumor-agnostic therapies encompass drugs targeting mutations/rearrangements in genes such as isocitrate dehydrogenase 1 (IDH1) [ 111 ], neurotrophic tropomyosin-receptor kinase (NTRK) [ 112 ], the V600E mutation of the BRAF gene (BRAFV600E) [ 113 ], and tumors with high tumor mutational burden, high microsatellite instability, and gene mismatch repair-deficiency (TMB-H/MSI-H/dMMR) [ 114 ]. Ongoing clinical trials are exploring HER2, RET, and non-BRAFV600E mutations in CCA, along with advancements in the efficacy and safety of new targeted treatments [ 9 ].…”

Section: The Role Of Eph/ephrin Signaling In Ccamentioning

confidence: 99%

Unraveling the Significance of EPH/Ephrin Signaling in Liver Cancer: Insights into Tumor Progression and Therapeutic Implications

Papadakos

Stergiou

Gkolemi

et al. 2023

Cancers

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Liver cancer is a complex and challenging disease with limited treatment options and dismal prognosis. Understanding the underlying molecular mechanisms driving liver cancer progression and metastasis is crucial for developing effective therapeutic strategies. The EPH/ephrin system, which comprises a family of cell surface receptors and their corresponding ligands, has been implicated in the pathogenesis of HCC. This review paper aims to provide an overview of the current understanding of the role of the EPH/ephrin system in HCC. Specifically, we discuss the dysregulation of EPH/ephrin signaling in HCC and its impact on various cellular processes, including cell proliferation, migration, and invasion. Overall, the EPH/ephrin signaling system emerges as a compelling and multifaceted player in liver cancer biology. Elucidating its precise mechanisms and understanding its implications in disease progression and therapeutic responses may pave the way for novel targeted therapies and personalized treatment approaches for liver cancer patients. Further research is warranted to unravel the full potential of the EPH/ephrin system in liver cancer and its clinical translation.

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“…Among the many alterations associated with pancreatic cancer, inactivation of TP53, SMAD4 and CDKN2A have been shown to occur in >50% of pancreatic ductal adenocarcinomas. 15,36,37 Carotenuto et al 38 review article discusses genomic alterations in cholangiocarcinoma, noting heterogeneity and complexity as well as large numbers of alterations are revealing complex patterns yet to be fully understood. We did have an unexplained amplification of CDKN2A in a cholangiocarcinoma but the significance is unclear.…”

Section: Smad4mentioning

confidence: 99%

The utilisation of digital droplet PCR to enhance the diagnosis of bladder and pancreaticobiliary tumours in cytology specimens

Weigner

Billings

Scott

et al. 2023

Diagnostic Cytopathology

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Background Digital droplet PCR (ddPCR) is a relatively new technique used to detect molecular alterations with unprecedented precision and accuracy. It is particularly useful for detecting point mutations and copy number variation (CNV) in samples with small amounts of target DNA. This proof of principle study was conducted to see if ddPCR technology could be applied to cytology specimens to detect molecular alterations which may influence diagnostic decision making. Methods A range of cytological specimens derived from bladder or pancreaticobiliary origin, with varying diagnoses but with an emphasis on abnormality, underwent ddPCR testing. DNA was manually extracted from Thinprep vials, cell blocks or direct fine needle aspiration smears. ddPCR was performed using two somatic point mutations TP53 R248W and TP53 R273H assays for both urine and pancreaticobiliary cytology specimens. Three CNV assays; CDKN2A, E2F3 and YWHAZ were applied to urine samples. SMAD4 and CDKN2A CNVs were applied to the pancreaticobiliary samples. Results 16 of 21 urine specimens showed molecular alterations using ddPCR testing. 12 of those 16 cases were associated with malignant outcomes. The pancreaticobiliary specimens showed 14 of 37 specimens with molecular alterations, all of which were associated with carcinoma. We demonstrated an increasing percentage of molecular aberrations associated with increasing severity of cytological results. Conclusion Our results have shown that ddPCR can identify both mutations and CNVs in urine and pancreaticobiliary cytology derived samples. Being able to detect these molecular alterations may reduce the number of equivocal results leading to more timely and informed patient management decisions.

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Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy

Cited by 15 publications

References 146 publications

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population

Unraveling the Significance of EPH/Ephrin Signaling in Liver Cancer: Insights into Tumor Progression and Therapeutic Implications

The utilisation of digital droplet PCR to enhance the diagnosis of bladder and pancreaticobiliary tumours in cytology specimens

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