This series of digital engagements highlights how targeting pathogenic gene fusions can improve patient outcomes:

The clinical utility of NRG1 fusions as a poor prognostic factor across tumor types, exploring NRG1+ tumors’ metastatic potential and histological features

Testing for NRG1 fusions in cancer patients, focusing on the importance of targeted NGS approaches and RNA-based NGS

As we conclude this series, catch-up on various activities so far:

 into the molecular biology of NRG1 fusions and explore its clinical relevance

to Dr Pranil Chandra discuss the clinical utility of NRG1 fusions and how to test for them using targeted NGS approaches and RNA-based NGS during the Lab Talk "Testing for NRG1 fusions: The new kid on the block of actionable pathogenic gene fusions"

key insights about RNA-NGS (RNA-based Next-Generation Sequencing) and its importance in detecting pathogenic NRG1 fusions

 the FAQs from the series and the slides from the Lab Talk. These can be printed for ease of reference.

 shed light on pathogenic gene fusions and the significant clinical utility of NRG1 fusions as key actionable pathogenic gene fusions which have been identified across many tumor types. The message highlighted the importance of comprehensive testing with RNA-based NGS being the optimal methodology to capture pathogenic gene fusions.

(Senior Vice President, Chief Genomics Officer, PathGroup), exploring NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions. To further support labs in NRG1 fusions testing Dr Chandra discussed how to properly test for NRG1 fusions in cancer patients, focusing on targeted NGS approaches and RNA-based NGS.

, and detecting them can improve patient outcomes.

RNA-NGS (RNA-based Next-Generation Sequencing)

 is more effective than DNA-only NGS in identifying actionable gene fusions.

Clinical guidelines (e.g., ESMO, ASCO) recommend RNA-NGS

 for detecting gene fusions, including NTRK fusions, due to its superior sensitivity.

 are emerging as actionable targets linked to poor prognosis, highlighting the importance of comprehensive RNA and DNA profiling.

RNA-NGS and DNA-NGS together enhances the detection of structural variants

, providing expanded therapeutic opportunities for patients.

Thank you for joining us throughout the series!

If you have any questions on this series or would like to learn more about the DXRX Network, contact help@dxrx.io.

Over the past few months, Diaceutics have delivered a series of digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.

The goal of Precision Medicine in oncology is to identify the right patient, for the right therapy, at the right time. 

Patient characteristics drive treatment decisions that are most likely to provide benefit.

Targeting pathogenic gene fusions can improve patient outcomes. 

In an analysis of 79 patients with identified gene fusions, poorer outcomes were observed in patients with pathogenic gene fusions who were not matched to an FDA-approved fusion-targeted therapy.

comprehensive profiling at the DNA and RNA levels (RNA-based NGS)

provide patients with therapeutic opportunities beyond standard treatments.

from PathGroup explored pathogenic gene fusions as oncogenic drivers and actionable biomarkers in precision oncology, focusing on NRG1 fusions. The session covered the 

 as a poor prognostic factor across tumor types, exploring 

 and histological features. Dr. Pranil Chandra from PathGroup also 

discussed how to properly test for NRG1 fusions in cancer patients

, focusing on targeted NGS approaches and RNA-based NGS.

defines cancer according to its genomic profile rather than by the organ or tissue of origin

select treatments most likely to benefit the patient

NRG1 is an important pathogenic gene fusion 

and is reported to be associated with poor outcomes

NRG1+ tumors possess aggressive histological features 

associated with increased tumor growth, invasiveness, 

recurrence, resistance to therapy, metastasis, and worse prognosis

Comprehensive testing with RNA-based NGS, including DNA and RNA sequencing, is recommended to detect NRG1 fusions

 due to its diversity of gene fusion partners and breakpoints and its large intronic region

Concurrent RNA-NGS and DNA-NGS testing should be used clinically to maximize structural variant detection relative to DNA-NGS alone

Click here to watch the Lab Talk recording now.

Thank you for joining us so far! Stay tuned for more insights on NRG1 fusions!

Download the testing for NRG1 fusions FAQs here.

Over the past couple of months, Diaceutics have delivered digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.

As we conclude this series, catch-up on various activities to:

about the clinical significance of FGFR3 alterations in bladder cancer

 discussing the clinical utility of FGFR3 alterations and technical challenges in the diagnostic journey of bladder cancer patients during the Lab Talk

 the FAQs and the slides from the Lab Talk for ease of reference

In the first Lab Alert, we highlighted that up to 20% of advanced urothelial carcinoma patients may have FGFR3 alterations, with FGFR3 mutations and fusions being predominant in bladder and upper tract urothelial tumors.

Accurate testing of the FGFR3 gene is crucial to ensure that eligible patients receive targeted therapies tailored to FGFR3 alterations.

Dr. Michael Hubank, Scientific Director, Clinical Genomics, Royal Marsden Hospital, London, which explored FGFR genomic alterations and their significance in bladder cancer. The session delved into FGFR3 clinical utility and the diagnostic journey for bladder cancer patients. Furthermore, Dr. Hubank emphasized the diagnostic pitfalls that labs should consider when testing for FGFR3 in bladder cancer. 

Thank you for joining our series. The slides from the Lab Talk are available to download by clicking the link below.

Download the Lab Talk slides

Helsten T et al. Clin Cancer Res 2016;22(1):259–267

Necchi A et al. Eur Urol Focus 2019;5(4):689–692

Over the past few months, Diaceutics have delivered a series of digital activities focused on the clinical significance of FGFR3 testing in bladder cancer. These digital engagements emphasized key learnings that can be incorporated into routine diagnostics to ensure timely and accurate identification of patients with FGFR3 alterations.

One of the activities was the Lab Talk led by Dr. Kurt Schalper from Yale School of Medicine, which explored NRG1 testing in cancer patients. The session covered the clinical utility of NRG1 fusions as a poor prognostic factor across tumor types, exploring NRG1+ tumors’ metastatic potential and histological features. Dr. Kurt Schalper also approached the challenges for detecting NRG1 fusions, considering that conventional methods often fail to detect these fusions. 

Key learnings from the series that can be implemented in routine diagnostics to ensure that patients with NRG1+ tumors are properly and timely identified:

Pathogenic gene fusions are key oncogenic drivers and actionable biomarkers in precision oncology

NRG1 fusions have been identified across many tumor types, with NRG1+ tumors being associated with aggressive features and poor outcomes in cancer patients

Conventional methods like RT-PCR, FISH, and IHC may fall short of detecting pathogenic gene fusions and have limitations in screening NRG1 fusions

Although NGS can detect a broad range of genomic alterations, DNA-based NGS alone can miss pathogenic gene fusions

Comprehensive testing with RNA-based NGS, including both DNA and RNA sequencing, is recommended to capture these fusions that DNA-based NGS might miss

The detection of NRG1 fusions is particularly difficult without RNA-based NGS due to the diversity of gene fusion partners, varying breakpoints, and large intronic regions

Proper testing for pathogenic gene fusions is necessary to maximize the identification of potentially eligible patients to benefit from targeted therapies

Poorer outcomes were observed in patients with pathogenic gene fusions who were not matched to an FDA-approved fusion-targeted therapy

Ultimately, RNA-based NGS can enable oncologists to match eligible patients with targeted therapy to the driving fusion, which wouldn’t have otherwise been identified, potentially leading to improved outcomes

Register interest

Thank you for joining us during our NRG1 fusions testing series!

Diaceutics organized a series of digital engagement activities focused on the clinical relevance of pathogenic gene fusions, specifically NRG1 fusions, for cancer patients.

NRG1 is a pathogenic fusion receiving increasing attention, as it is associated with multiple poor prognostic factors

 NRG1 fusions are genetic alterations that involve the NRG1 gene being abnormally fused with another gene. These fusions are heterogeneous and have many different gene partners and breakpoints. NRG1 fusions result in increased cell signaling and growth and can lead to uncontrolled growth and cancer.

NRG1 fusions have been identified across many tumor types and generally occur in the absence of other driver mutations. The overall frequency of NRG1 fusions varies across tumor types, with the highest being found in lung cancer (0.3%-1.7%) and pancreatic cancer (0.5%-1.8%), with other tumor types having <1%.

Importantly, there is a significant enrichment in NRG1 fusions in invasive mucinous lung adenocarcinoma (27%-31%) and in KRAS wild-type pancreatic cancer (up to 6%).

Methods like RT-PCR, FISH, and IHC may fall short of detecting pathogenic gene fusions and have limitations in screening NRG1 fusions. Detection of NRG1 fusions poses challenges, as DNA-based NGS alone can miss pathogenic gene fusions and lead to false-negative and false-positive results. Comprehensive testing with RNA-based NGS, including both DNA and RNA sequencing, is recommended to capture these fusions that DNA-based NGS might miss. The detection of NRG1 fusions is particularly difficult without RNA-based NGS due to the diversity of gene fusion partners, varying breakpoints, and large intronic regions.

To learn more about NRG1 fusions and RNA-based testing please visit

Next week we will be inviting you to join our latest Lab Talk with Dr. Kurt Shalper from Yale School of Medicine. During this session Dr. Shalper will discuss pathogenic gene fusions as oncogenic drivers and actionable biomarkers in precision oncology, focusing on NRG1 fusions.

1. Gao Qet al. Cell Rep. 2018;23(1):227-238.e3. doi:10.1016/j.celrep.2018.03.050. 2. Latyshevaet al.Nucleic Acids Res. 2016;44(10):4487-4503. doi:10.1093/nar/gkw282. 3. Heyer EEet al. Nat Commun. 2019;10(1):1388. doi:10.1038/s41467-019-09374-9. 4. Liu SV. Future Oncol. 2022;18(26):2865-2870. doi:10.2217/fon-2022-0073. 5. Drilon Aet al. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307. 6. Rosas D et al. Cancers (Basel). 2021;13(20):5038. doi:10.3390/cancers13205038. 7. Laskin J et al. Ann Oncol. 2020;31(12):1693-1703. doi:10.1016/j.annonc.2020.08.2335. 8. Zhang C et al. BiochimBiophys Acta Rev Cancer. 2022;1877(3):188707. doi:10.1016/j.bbcan.2022.188707. 9. Drilon A et al. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307. 10. Schram AM et al. Cancer Discov. 2022;12(5):1233-1247. doi:10.1158/2159-8290.CD-21-1119. 11. Geuijen CAW et al. Cancer Cell. 2018;33(5):922-936. doi:10.1016/j.ccell.2018.04.003. 12. Liu SV. Plain language summary of NRG1 fusions in cancer: current knowledge and treatment with afatinib and other drugs. Future Oncol. 2022;18(26):2865-2870. doi:10.2217/fon-2022-0073. 13. Drilon A, Somwar R, Mangatt BP, et al. Response to ERBB3-directed targeted therapy in NRG1-rearranged cancers. Cancer Discov. 2018;8(6):686-695. doi:10.1158/2159-8290.CD-17-1004. 14. Jones MR et al. Clin Cancer Res. 2019;25(15):4674-4681. doi:10.1158/1078-0432.CCR-19-0191. 15. Liu SV et al. Future Oncol. 2022;18(26):2865-2870. doi:10.2217/fon-2022-0073. 16. Drilon A et al. Cancer Discov. 2018;8(6):686-695. doi:10.1158/2159-8290.CD-17-1004. 17. Jones MR et al. Clin Cancer Res. 2019;25(15):4674-4681. doi:10.1158/1078-0432.CCR-19-0191. 18. Bruno R et al. Diagnostics (Basel). 2020;10(8):521. doi:10.3390/diagnostics10080521. 19. Su D et al. J Exp Clin Cancer Res. 2017;36(1):121. doi:10.1186/s13046-017-0591-4. 20. Benayed R et al. Clin Cancer Res. 2019;25(15):4712-4722. doi:10.1158/1078-0432.CCR-19-0225. 21. Heydt C et al. BMC Med Genomics. 2021;14(1):62. doi:10.1186/s12920-021-00909-y

Fusions can occur across different tumor types, being a contributing factor in 1 in 6 cancers and accountable for approximately 20% of cancer morbidity. Among 9624 patients who had their tumors genetically tested with RNA-based sequencing, pathogenic gene fusions were found in 16.5% of samples.

FGFR3 alterations play a pivotal role in the development and progression of bladder cancer. Its frequent mutations and fusions make it a key biomarker for targeted therapy in bladder cancer patients.

FGFR inhibitors have shown efficacy in treating FGFR3-altered urothelial cancer

, but identifying patients who will benefit most from FGFR3-targeted therapies requires reliable and comprehensive molecular testing.

Gene mutations and fusions of FGFR3 are important for diagnosing bladder cancer. As such, RNA samples may be required. Tissue biopsy (TURBT - transurethral resection of urothelial tumour) is the gold standard for FGFR3 testing in metastatic urothelial carcinoma.

 However, TURBT can result in heterogeneous samples, thus impacting the tissue quality available for biomarker testing. If fresh biopsies are not feasible, tumor tissues archived via formalin fixed and paraffin embedded (FFPE), using fresh or flash frozen methods from diagnosis can be used. 

Additionally, urine testing (urine cytology and tissue marker tests) has the potential to assist in clinical decision-making due to its ease of sampling, potentially reducing the need for invasive procedures.

There are 3 major diagnostic pitfalls that labs should consider when testing for FGFR3 in bladder cancer:

 The choice of test may depend on the clinical context, available resources, and specific FGFR3 alterations of interest. For instance, NGS provides comprehensive data but may not be necessary for detecting a known single mutation, where RT-PCR could suffice.

 The accuracy of FGFR3 testing depends on the quality of the sample. Adequate tumor content in tissue biopsies or sufficient DNA/RNA quantity and quality from urine samples are essential.

 Positive results for FGFR3 genetic alterations can help in prognostication and selecting patients for FGFR-targeted therapies. Negative results, particularly from highly sensitive methods like NGS or RT-PCR, mean a patient is not eligible for the targeted therapy.

1. Helsten T et al. Clin Cancer Res 2016;22(1):259–267. 2. Necchi A et al. Eur Urol Focus 2019;5(4):689–692. 3. Wang Z et al. npj Precis Onc 2023;7(70). 4. Benjamin DJ et al. Front Immunol. 2023;14:1258388. 5. Mazzucchelli R et al. Front Surg. 2021 Dec 2;8:754741.

                                                Approval code: EM-162587

Up to 20% of patients with advanced urothelial carcinoma may have FGFR alterations, with FGFR3 mutations and fusions being predominant in bladder and upper tract urothelial tumours.

The prevalence of FGFR3 mutations and fusions is approximately 80% in non-muscle-invasive bladder cancer (NMIBC) patients, compared to 20% in muscle-invasive bladder cancer (MIBC) patients.

 To ensure eligible patients receive targeted therapies specific to FGFR3 alterations, accurate testing of FGFR3 gene is essential.

Insights

Testing for NRG1 Fusions - The Series

Testing for NRG1 Fusions Series So Far

Catch-up on the series: FGFR3 testing in bladder cancer

Catch-up on the series: NRG1 fusions testing

Pathogenic gene fusions are key actionable biomarkers in precision oncology

The clinical relevance of FGFR3 testing in bladder cancer