SpaceGen LunyboTM non-small cell lung cancer 13-gene DNA+RNA synchronous co-detection, based on consensus, achieves both quality and effectiveness

SpaceGen LunyboTM non-small cell lung cancer 13-gene DNA+RNA synchronous co-detection, based on consensus, achieves both quality and effectiveness

1.Preface

*Chinese Journal of Lung Cancer* Releases the World's First Expert Consensus on DNA+RNA Synchronous Co-detection of Non-Small Cell Lung Cancer

In November 2023, the "Expert Consensus on Clinical Practice of Fusion Genes in Non-Small Cell Lung Cancer Based on RNA-based NGS Detection" (hereinafter referred to as the "Consensus") was officially published in the *Chinese Journal of Lung Cancer*. The Consensus was initiated by the Tumor Precision Diagnosis and Treatment Professional Committee of the China Primary Health Care Foundation and other associations. Professors Han Baohui from Shanghai Jiao Tong University Affiliated Chest Hospital, Lin Dongmei from Peking University Cancer Hospital, Zhou Qinghua from West China Hospital of Sichuan University, Song Yong from the Eastern Theater General Hospital, Zhou Xiaoyan from Fudan University Affiliated Cancer Hospital, and Zhou Qing from Guangdong Provincial People's Hospital Tumor Hospital jointly served as guiding experts for compilation. Professor Zhong Hua from Shanghai Jiao Tong University Affiliated Chest Hospital took the lead, and more than 60 clinical pathology experts from all over the country participated in discussions, revisions, voting, and finalization, formulating this expert consensus that, for the first time among domestic and international guidelines, recommends the simultaneous detection of non-small cell lung cancer driver genes using DNA in conjunction with RNA.

In the past two to three years, many technologies and products for the clinical application of DNA and RNA co-detection fusion have been developed. However, due to the fact that most of these technologies and products independently perform DNA and RNA sequencing on tumor samples, the detection costs are high, and the sample requirements are stringent, hindering widespread use. Currently, the technology of DNA-based NGS combined with RNA-based NGS for one-time synchronous detection of gene mutations and fusions has been successfully developed and applied in clinical practice. However, in China, there is still a lack of norms and standards for the application timing, application scenarios, and quality control of RNA-based NGS detection of fusion genes. As the world's first expert consensus on DNA+RNA synchronous co-detection of non-small cell lung cancer, this consensus will further clarify the application timing, application scenarios, and quality control of RNA-based NGS in fusion gene detection. It will provide guiding recommendations and promote the one-time synchronous detection of DNA-based NGS combined with RNA-based NGS in the clinical diagnosis and treatment of non-small cell lung cancer, maximizing the benefits for patients from fusion gene detection.

2. Overview of Consensus

Consensus 1: Compared to DNA-based Next-Generation Sequencing (NGS), RNA-based NGS is not influenced by introns and can enhance the detection rate of fusion genes. It is recommended that qualified medical institutions perform simultaneous RNA-based NGS and DNA-based NGS testing for driver gene variations (fusion/mutation) in NSCLC samples. [Strongly recommended]

Consensus 2: Currently, RNA-based NGS can be used to detect fusion genes of driver genes such as ALK, RET, ROS1, NTRK, NRG1, and MET. [Strongly recommended]

Consensus 3: Fusion genes detected by RNA-based NGS can guide targeted therapy related to NSCLC fusion mutations. [Strongly recommended]

Consensus 4: RNA-based NGS can be applied to all NSCLC populations, and it is also recommended to pay more attention to lung cancer patients with a higher correlation to the frequency of fusion genes (such as adenocarcinoma, females, non-smokers, rapidly progressing tumors, etc.). [Strongly recommended]

Consensus 5: FFPE samples, after passing quality control assessments, can be used for RNA-based NGS to detect fusion genes. [Strongly recommended]

Consensus 6: The detection of fusion genes by RNA-based NGS should thoroughly evaluate quality control information such as tumor cell content, RNA integrity, library yield, and purity. Qualified medical institutions should issue RNA-based NGS testing reports. [Strongly recommended]

3. Clinical Significance of RNA-based NGS

01. Increased Detection Rate of Fusion Genes with RNA-based NGS

Both domestic and international guidelines for the diagnosis and treatment of non-small cell lung cancer (NSCLC) unanimously recommend the testing of fusion genes, including ALK, ROS1, RET, and NTRK. The NCCN guidelines explicitly state that RNA-based NGS can improve the detection rate of MET exon 14 skipping mutations. However, DNA-based NGS can miss up to 18% of cases with MET exon 14 skipping mutations. In situations where DNA-based NGS does not detect fusion genes, RNA-based NGS can enhance the detection rate of fusion genes.

02. RNA-based NGS Screens for a Larger Population Benefiting from Targeted Therapies

In patients with negative driver gene results from DNA-based NGS testing, RNA-based NGS can identify 10%-14.2% additional individuals with actionable fusion mutations. Current guidelines from CSCO and NCCN typically recommend immune monotherapy or combination therapy for first-line treatment in patients with negative driver gene results. However, existing research data indicate that the progression-free survival (PFS) and overall survival (OS) of NSCLC patients receiving first-line immune therapy are still inferior to those receiving first-line targeted therapy related to fusion genes.

Therefore, the NGS testing method combining DNA and RNA significantly improves detection efficiency, expands the population eligible for targeted therapies, and the "one-tube dual-testing" technology reduces the cost of testing, improves accessibility, and brings more benefits to patients.

4. LunyboTM DNA+RNA Synchronous Co-detection, Assisting Precision Diagnosis and Treatment

As a medical testing and diagnostic service enterprise, SpaceGen is at the forefront of introducing a precise tumor diagnostic solution, "DNA+RNA co-detection in one tube, more accurate, more comprehensive." Its independently developed LunyboTM non-small cell lung cancer 13-gene test combines DNA and RNA testing, enabling more accurate detection of various gene mutations, including fusions, benefiting more cancer patients from targeted therapy.

01 Comprehensive Testing Types

Covering 13 genes and 482 types of somatic cell mutations, including EGFR, MET, HER2, AKT1, KRAS, BRAF, PIK3CA, NRAS, KIT, PDGFRA, ALK, RET, ROS1, the test includes single-base mutations, insertions, deletions, and gene fusion mutations.

02 True Synchronous Detection

This reagent kit combines specific modified primers and the RingCap® loop-mediated isothermal amplification technology on a regular PCR platform to detect mutated genes in nucleic acid samples. Utilizing specific modified primers for precise PCR amplification of target sequences, and simultaneously using the RingCap® loop-mediated isothermal amplification technology to modify the ends of the amplification products, connecting specific sequence ends. Through the use of a special PCR reaction program, linking enzymes, and the highly specific RingCap-Taq enzyme, the kit achieves accurate and rapid detection of multiple gene mutations at multiple target points for library construction suitable for high-throughput sequencing on a regular PCR platform.

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