At AACR 2025, Geneseeq will showcase seventeen posters from both internal research and collaborative efforts, spanning minimal residual disease (MRD), cancer genomics, biomarker identification, and treatment response—reinforcing our commitment to innovation and excellence across multiple domains, from discovery to clinical impact.

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Highlights of these studies include:

• Data on Geneseeq’s new algorithms based on cfDNA fragmentomics features to predict the outcomes of prostate cancer patients as well as to detect lung cancer brain metastases, pulmonary malignancy, and disease progression.
• Two large cohort studies unraveled the landscape of pathogenic/likely pathogenic germline alterations at pan-cancer scale and lung cancer scale.
• Multi-omics analysis of rare cancer populations including fetal adenocarcinoma of the lung and acral melanoma.

List of abstracts that will be presented at the AACR 2023 meeting:

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ePoster 5336 Dissecting the molecular mechanism of trastuzumab resistance in stage IV HER2-positive gastric cancer patients.

Theme: Drug Resistance

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17633

Study highlights: Trastuzumab-resistance-associated gene alterations in stage IV HER2-positive gastric cancer

The effect of trastuzumab in targeted therapy for HER2-positive gastric cancer (GC) is limited by the eventual development of resistance within patients. Although numerous studies have been published on this topic, both the mechanism of innate and acquired trastuzumab resistance are still not fully understood. In this study, we performed whole-exome sequencing on 46 tumor and 23 whole blood samples from patients with stage IV gastric cancer were obtained before treatment (n = 23) and at disease progression (PD) (n = 23). HER2 status was checked using immunohistochemistry and validated with florescence in situ hybridization (FISH). Overall, our results show that comparisons of samples obtained before treatment and at PD can give insight about innate and acquired resistance mechanisms to trastuzumab in stage IV, HER2-positive GC patients.

ePoster 5765 Genomic characterization of Chinese biliary tract cancers identifies differences between subtypes and therapeutic biomarkers

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17883

Study highlight:  Distinct genomic features are revealed among different biliary tract cancers subtypes

Biliary tract carcinoma (BTC) is a relatively rare cancer worldwide and accounts for 3% of gastrointestinal cancers in China. BTCs are mainly classified as gallbladder cancer (GBC) and cholangiocarcinomas (CCA) with dismal prognosis. We analyzed 258 BTC tissure samples including 70 GBCs and 188 CCAs with targeted sequencing (NGS) using a 425 cancer-relevant genes panel. The present study aims to compare the molecular features between BTC subtypes and explore clues for treatment therapies.

ePoster 5766 Pan-cancer analysis revealed characteristics of reversion mutations in homologous recombination repair (HRR) genes

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17884

Study highlight: In-depth analysis of HRR genes reversion mutations in pan-cancer population

Reversion mutations of BRCA1/2 are associated with decreased response to platinum-based chemotherapies and PARP inhibitors. While patients with homologous recombination repair (HRR) genes have proven efficacy in PARP inhibitors, reversion mutations in these genes have not been widely studied. Here, we performed pan-cancer analyses to reveal the characteristics of HRR reversion mutations. This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors.

ePoster 5767 Landscape of concomitant driver mutations in EGFR-mutated NSCLC

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17885

Study highlight: Retrospective study of co-existing driver mutations in a large EGFR-mutated NSCLC cohort

While most oncogenic driver mutations are mutually exclusive, next-generation sequencing (NGS) has led to the identification of concomitant driver alterations in non-small cell lung cancer (NSCLC). However, the landscape of concomitant drivers and the clinical relevance remain to be explored. We profiled concomitant driver alterations, including EGFR, KRAS, ALK, RET, ROS1, MET, BRAF and ERBB2 from baseline tumor
tissues of 22,610 NSCLC patients by using targeted NGS. The associated genomic and clinical features were analyzed and validated in a TCGA dataset of 136 EGFR+ NSCLC patients. In our large cohort study, we present the landscape of EGFR+ dual drivers and their associated clinical and genomic features and survival outcomes, which could aid in therapeutic decisions and facilitate the development of combination therapies.

ePoster 5768 Genomic characteristics of classic and uncommon EGFR (uEGFR) activating mutations explain different responses to first-generation EGFR-TKIs

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17886

Study highlight: Comprehensive genomic evaluation of uEGFR-positive NSCLC

Classic sensitizing mutations of epidermal growth factor receptor (cEGFR) (i.e., exon 19 deletions and exon 21 L858R) have shown positive responses to first-generation TKIs in non-small cell lung cancer (NSCLC). For patients with uncommon EGFR mutations (uEGFR), such as G719X, S768I, L861Q and exon 20 insertions, first-generation TKIs might still be one of the mainstay choices in the clinic. However, they exhibited heterogeneity in treatment responses. Here, we aimed to elucidate different genomic profiles of tumors carrying uncommon EGFR activating mutations to explain differential treatment responses. We screened 6669 NSCLC patients that underwent targeted NGS of 416 cancer-related genes. This comprehensive analysis of EGFR-positive mutational landscape revealed specific genomic characteristics associated with uncommon EGFR mutations that might explain their poor response to first-generation TKIs.

ePoster 5772 Differences in clinical actionability by comparing mutational landscape of young and old breast cancer patients

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/17890

Study highlight: Identification of age-related gene alterations in breast cancer

Early-onset breast cancer (BC) is associated with poor prognosis, which is also characterized by high recurrence risk, distant metastases and advanced stages at the time of diagnosis. While germline mutations in BRCA1/2 are known to underlie a subset of early-onset BC cases, the clinical and genetic characteristics in other young BC patients remain to be explored. We profiled primary lesions from 440 Chinese female BC patients by using a 425-cancer-gene panel. BC in young and old patients exhibited different genomic characteristics that could be taken into consideration for treatment recommendations.

ePoster 5781 Molecular positive margin of surgical resections is a strong biomarker for tumor recurrence in pIIIA-N2 NSCLC patients

Theme: Genomics

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/18793

Study highlight: The utility of molecular positive margin in predicting lung cancer recurrence

The high recurrence rate of stage pIIIA-N2 NSCLC patients may reflect inadequate removal of all residual tumor cells despite conventional histologic negative surgery margin. The NGS-detected BRM status was possible to serve as a more accurate examination to identify those patients with a high risk of postoperative recurrence. We retrospectively studied 119 stage IIIA-N2 NSCLC patients who received curative-intent surgery plus adjuvant chemotherapy/chemoradiotherapy using next-generation sequencing (NGS) of 474 cancer-related genes. Our results emphasized the clinical utility of molecular diagnostic approaches to detect minimal residual disease after surgical resection, which could potentially facilitate the stratification of high-risk patients for personalized and appropriate treatments.

ePoster 6054 Genomic and transcriptomic remodeling of esophageal squamous cell carcinoma (ESCC) by neo-adjuvant radiochemotherapy (nCRT)

Theme: Radiation Science

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/18064

Study highlight: Multiomics interpretation of nCRT biomarkers in ESCC

To identify genetic and clinicopathological factors that affect the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), profile the genomic and transcriptomic alterations after nCRT and relate the alterations to the patient’s prognosis. A total of 137 samples from 57 ESCC patients undergoing nCRT were collected. 82 samples including 54 pre-treatment samples and 28 post-treatment samples were subjected to whole-exome sequencing, and 55 samples including 26 pre-treatment samples and 29 post-treatment samples were subjected to RNA-seq analysis. This study shows that acquired INDEL proportion is a biomarker to indicate the efficacy of nCRT and predict patient’s prognosis. The degree of clonal expansion during nCRT reflects the treatment resistance and is associated with the patient’s prognosis.

ePoster 6117 Clinical and molecular correlates of immune marker profiling and PD-L1 expression in non-small cell lung cancer (NSCLC)

Theme: Tumor Microenvironment

Link: https://www.abstractsonline.com/pp8/#!/10517/presentation/18036

Study highlight: Combination of NGS and mIHC approach for identifying immune biomarkers associated with disease outcomes in NSCLC

Understanding the genomic landscape and tumor immune microenvironment of non-small cell lung cancer (NSCLC) may provide critical insight into the biology of tumor immune response and novel strategies for overcoming immunotherapy resistance. The association of clinical and genomic features with tumor immune microenvironment in NSCLC patients remains unclear. In this retrospective cohort study, we profiled
PD-L1 and immune cell marker expressions and performed targeted next-generation sequencing of baseline tissue samples from 100 NSCLC patients. The levels of CD8+, CD68+ and HLA-DR+ immune cells were assessed by multiplexed immunohistochemistry (mIHC) assay. Our study demonstrates the complex relationship between gene mutations and aberrations in signaling pathways with the immune microenvironment in NSCLC. Specific molecular features are associated with unique immune profiles and may impact the response to immune checkpoint inhibitors

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