TORONTO, April 9 — The American Association for Cancer Research (AACR) is the earliest and largest professional cancer research association in the world, dedicated to basic cancer science and clinical research. The 2021 AACR annual meeting will be held on April 10-15 and May 17-21 virtually. Geneseeq has participated in the Annual Meeting of AACR, ASCO, ESMO, WCLC, and other international conferences for seven consecutive years and has so far shared nearly a hundred translational research studies. At this year’s AACR Annual Meeting, there will be five posters published by Geneseeq and Collaborators. The posters summarize our research in the analysis of rare genomic alterations and novel biomarkers for precision oncology.

ePoster session number: 2166

The prevalence and molecular characteristics of EGFR large fragment deletion in Asian cancer population by comprehensive genome profiling

Study highlight: Retrospective analysis of large patient cohort reveals the incidence and molecular characteristics of large EGFR fragment deletions

Large EGFR fragment deletion (LFD) is associated with a variety of cancers, especially glioblastoma. Studies have shown that there are five major types of EGFR deletions that span the extracellular region and the carboxy-terminal domain of EGFR in gliomas. However, there are still few studies on the incidence rate and molecular characteristics of EGFR-LFD in Asian cancer patients. This study retrospectively analyzed tens of thousands of tumor tissue samples from cancer patients that were tested by Geneseeq’s GENESEEQPRIME® 425-pan cancer gene panel and found that the detection frequency of EGFR-LFD was 0.03%. The most common type in glioblastoma is EGFRvIII, while new types of EGFR-LFD across exon2-7 have been found in other cancers, including EGFR exon2-11 (1 case, lung cancer), exon2-15 (1 case, lung cancer), exon2-17 (2 cases, lung cancer, and colorectal cancer), exon2-28 (1 case, cholangiocarcinoma). TERT promoter variants occur most frequently in EGFR-LFD carriers (60%). 67% of patients in the EGFR-LFD cohort carry EGFR amplification at the same time, and more than half of the EGFR-LFD carriers have deletions on both arms of chromosome 10.

ePoster session number: 2210

Chromosome arm aneuploidy landscape in lung adenocarcinoma

Study highlight: In-depth analysis of chromosomal arm aneuploidy of lung adenocarcinoma and its correlation with driver mutations

Aneuploidy, including the imbalance of the entire chromosome or chromosome arm, is considered a common feature of all cancers. Previous studies have shown that chromosomal arm aneuploidy (CAA) may affect processes such as tumor evolution, cancer metastasis, patient survival, and drug response. In this study, a total of four types of CAA analysis were performed in 3533 lung adenocarcinoma patients, including: total CAA burden, increase-decrease patterns, coexistence/exclusion, and population CAA levels, aiming to analyze specific CAA patterns in patients with primary tumors, different metastases, and different driver mutations in lung adenocarcinoma. It also evaluates the correlation between CAA and driving mutations. Analysis of the potential biological significance of CAA patterns may be an effective predictor of clinical outcome, with further research needed to support the findings.

ePoster session number: 2249

Molecular landscape and actionable alterations in Chinese soft-tissue sarcoma patients

Study highlights: Soft tissue sarcoma genomic profiling hints for targeted therapy and immunotherapy. 

Soft tissue sarcoma (STS) is a rare malignant tumor, divided into multiple subtypes based on its tissue origin. Limited by the number of different subtypes and pathological conditions, it is difficult to conduct large-scale clinical trials on STS patients. At present, drug-related research on STS targeted therapy is still in preclinical and early trials. In order to study the potential of targeted therapy in STS, this study analyzed the genomic profiles of 351 Chinese STS patients with different tissue subtypes for their mutational variants, CNV, TMB, MSI and HRD using Geneseeq’s GENESEEQPRIME® 425-pan cancer gene panel test. A total of 2743 variants of 330 genes were detected in this study with the top 10 genes with high mutation frequency being TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B and FGFR1; high-frequently mutated pathways include: RTK-RAS (59%), TP53 (53%) , cell cycle (39%) and PI3K (38%). TMB-High accounted for approximately 9.40% of the patients, whereas 2.9% are MSI, and 13.7% are HRD positive. According to OncoKB’s definition, 242 actionable mutations were found in 23 genes in 43% of the patients.

ePoster session number: 2211

The landscape and implications of kinase-intergenic fusions in a large real-world lung cancer cohort 

Study highlight: Analysis of potential carcinogenicity of kinase gene fusions. 

The fusion of kinase genes is a strong driver mutation in tumor formation and one of the important mechanisms of tumorigenesis. Many studies have described fusion events where breakpoints occur in two genes, but kinase fusions with intergenic regions without obvious fusion partner genes identified by next-generation sequencing technology are not uncommon, and the clinical significance of such fusions needs to be studied in depth. This study retrospectively analyzed the tissue and/or plasma samples of more than tens of thousands of lung cancer patients. Using GENESEEQPRIME® 425-pan cancer panel, a total of 624 kinase-intergenic fusion events were identified in 538 lung cancer patients. About 75% were non-small cell lung cancer (NSCLC), and 93% were lung adenocarcinoma. Kinase genes with higher detection rates include ALK, RET, ROS1, ERBB2/3, EGFR, FGFR1/2/3 and NTRK1/2/3. 67% of kinase-intergenic region fusions occur on the same chromosome of the kinase, and the kinase domain remains intact. 167 patients had only detectable kinase-intergenic fusions and no other known oncogenic driver mutations. It is worth noting that 4 patients with ALK-intergenic fusions were later validated as EML4-ALK fusions by RNA sequencing and/or immunohistochemistry (IHC). One of the patients was treated with crizotinib and achieved a 14-month durable response, while another patient achieved a SD of 5 months on crizotinib. Two more patients with ROS1-intergenic fusions maintained SD for 11 and 19 months, respectively. This study highlighted that lung cancer patients with oncogenic gene kinase-intergenic fusions could potentially benefit from targeted therapy.

ePoster session number: 2041

Genetic profiling of DNA damage repair genes in hepatobiliary cancer

Study highlight: FGFR fusion may be one of the secondary resistance mechanisms of EGFR-TKIs

Hepatobiliary cancer has strong genetic and clinical heterogeneity. At present, the benefits of precision medicine of hepatobiliary cancer are limited. New biomarkers are needed to improve the clinical benefits of hepatobiliary cancer patients. In this study, next-generation sequencing was used to map mutational profiles of the tumor samples from 379 patients with hepatocellular carcinoma (HCC) and 490 patients with biliary tract cancer (BTC), and analyzed the non-synonymous mutations, copy number variants (CNV), Tumor mutation burden (TMB) and signal pathway enrichment. Analysis of HCC and BTC somatic mutation pathways showed that mutations in DNA damage repair (DDR) pathways (including TP53) are enriched, and more than 70% of patients have found such DDR mutations.  Mutations in homologous recombination repair (HRR), mismatch repair (MMR) and base excision repair (BER) pathways were significantly associated with high TMB (p<0.001). Interestingly, compared with HCC, mutations carried in BTC patients who engage in TMB are related to Fanconi anemia and cell cycle checkpoint pathways (p<0.001). In addition, gallbladder cancer showed high levels of BRCA2 mutations (6.3%). These results potentially shed more light for targeted therapy or immunotherapy of liver and gallbladder cancers.

Through large-scale NGS testing combined with clinical characteristics and treatment history, a comprehensive analysis of the incidence and mutational characteristics of gene mutations in cancer patients can provide more clinical evidence for precision oncology. Geneseeq has tested more than 420,000 tumor samples and accumulated large amount of clinical research data for the treatment of rare mutations. Beyond the conclusion of this year’s AACR Annual Meeting, Geneseeq looks forward to cooperating with more experts and jointly promote the development of precision oncology.