Abstract 1603
Background
The responses and benefit from targeted therapies in gastric cancer (GC) remain limited and improved biologic understanding is needed. Both inter-tumoral and intra-tumoral heterogeneity for HER2 and EGFR has been observed in small datasets and may limit efficacy of targeted therapies. Broader heterogeneity assessment has not been studied. We sought to explore intra-tumoral heterogeneity in GC by multi-region sampling of primary gastric tumors with subsequent interrogation of mutational differences via next generation sequencing (NGS) and cell-free DNA (cfDNA) analyses.
Methods
Patients with newly diagnosed advanced GC underwent endoscopic mapping and pre-determined 8-region biopsy of the primary with concurrent plasma cfDNA sampling. Biopsy samples were subjected to NGS using a 32-gene custom panel and plasma cfDNA analyzed via 28-gene cfDNA assay. Clinicopathologic features and genomic alterations (GA) were abstracted and descriptive statistics were used to compare samples.
Results
All six initial patients underwent multi-region biopsy and NGS. Within a given patient the average number of GA observed in all biopsies (shared GA) was 3.3 with an average of 12.8 non-shared alterations (p = < 0.05). There was no significant difference in the average mutant allele frequency (MAF) or MAF variability between shared and non-shared GA in the primary tumor (p = > 0.05). Cell free DNA analyses identified GA not found in each respective case’s multi-region primary tumor analysis, likely reflective of GA derived from metastatic sites. An updated cohort will be presented.
Conclusions
Endoscopic multi-region biopsy of GC is feasible and significant genomic heterogeneity existed within the primary in all patients. Paired cfDNA analyses should also be included to complement studies of intra-tumoral heterogeneity. Standardized methods to determine intra and inter-tumoral heterogeneity are needed and stratification by heterogeneity score in prospective trials may inform optimal patient selection, particularly in targeted therapies.
Clinical trial identification
Legal entity responsible for the study
Samsung Medical Center.
Funding
Samsung Medical Center.
Editorial Acknowledgement
Disclosure
S.J. Klempner: Consulting, Advisory: Lilly Oncology, Boston Biomedical, Astellas, Merck. J. Chao: Consulting, Advisory: Boston Biomedical, Merck, Five Prime Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
1159 - Molecular characterization and search for founding effects in Canarian families with Hereditary Breast and Ovarian Cancer Syndrome
Presenter: Elisenda Llabres Valenti
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3725 - Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population. Modulation by gender
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3708 - Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5057 - Association of a genetic variant in cyclin-dependent kinase Inhibitor 2A gene with the increased risk of breast cancer
Presenter: Soodabeh Shahid Sales
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5970 - Investigating the role of HAT protein TIP60 in regulating functional dynamics of nuclear receptor PXR
Presenter: KARISHMA BAKSHI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1360 - The role of downregulated SIRT3 expression in patients with hepatocellular carcinoma
Presenter: Hanhee Jo
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1634 - Prediction and Intervention of Colorectal Cancer Risk with Artificial Intelligent System
Presenter: Yang Ge
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4921 - Measuring the Efficiency of Cancer Care in Europe
Presenter: Rikard Althin
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1235 - Circulating cell-free DNA isolated from plasma of mesenteric veins predicts prognosis in stage II colorectal cancer patients
Presenter: Chih-Yung Yang
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5169 - _lonality of uterine carcinosarcoma as a factor of clinical prognosis.
Presenter: Natalia Levitskaya
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract