TY - JOUR T1 - Spatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination JF - Gut JO - Gut SP - 1823 LP - 1832 DO - 10.1136/gutjnl-2020-320805 VL - 70 IS - 10 AU - Raghav Sundar AU - Drolaiz HW Liu AU - Gordon GA Hutchins AU - Hayley L Slaney AU - Arnaldo NS Silva AU - Jan Oosting AU - Jeremy D Hayden AU - Lindsay C Hewitt AU - Cedric CY Ng AU - Amrita Mangalvedhekar AU - Sarah B Ng AU - Iain BH Tan AU - Patrick Tan AU - Heike I Grabsch Y1 - 2021/10/01 UR - http://gut.bmj.com/content/70/10/1823.abstract N2 - Objective Endoscopic mucosal biopsies of primary gastric cancers (GCs) are used to guide diagnosis, biomarker testing and treatment. Spatial intratumoural heterogeneity (ITH) may influence biopsy-derived information. We aimed to study ITH of primary GCs and matched lymph node metastasis (LNmet).Design GC resection samples were annotated to identify primary tumour superficial (PTsup), primary tumour deep (PTdeep) and LNmet subregions. For each subregion, we determined (1) transcriptomic profiles (NanoString ‘PanCancer Progression Panel’, 770 genes); (2) next-generation sequencing (NGS, 225 gastrointestinal cancer-related genes); (3) DNA copy number profiles by multiplex ligation-dependent probe amplification (MLPA, 16 genes); and (4) histomorphological phenotypes.Results NanoString profiling of 64 GCs revealed no differences between PTsup1 and PTsup2, while 43% of genes were differentially expressed between PTsup versus PTdeep and 38% in PTsup versus LNmet. Only 16% of genes were differently expressed between PTdeep and LNmet. Several genes with therapeutic potential (eg IGF1, PIK3CD and TGFB1) were overexpressed in LNmet and PTdeep compared with PTsup. NGS data revealed orthogonal support of NanoString results with 40% mutations present in PTdeep and/or LNmet, but not in PTsup. Conversely, only 6% of mutations were present in PTsup and were absent in PTdeep and LNmet. MLPA demonstrated significant ITH between subregions and progressive genomic changes from PTsup to PTdeep/LNmet.Conclusion In GC, regional lymph node metastases are likely to originate from deeper subregions of the primary tumour. Future clinical trials of novel targeted therapies must consider assessment of deeper subregions of the primary tumour and/or metastases as several therapeutically relevant genes are only mutated, overexpressed or amplified in these regions.All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request: Please contact PI Heike Grabsch. ER -