Oncology - Breast Cancer Spatial Transcriptomics

Dr. Annette Lasham is a senior research fellow in the Department of Molecular Medicine and Pathology at the University of Auckland (Waipapa Taumata Rau). Along with Dr. Nicholas Knowlton, she co-leads the Digital Cancer Group, which works on a number of transformative studies with the ultimate goal of improving the diagnosis, treatment and outcomes for people with breast cancer in Aotearoa New Zealand.

The Digital Cancer Group works on the following:
-Breast cancer 'omics'
-Ductal Carcinoma in situ (DCIS)
-Breast cancer in young women- "Helena McAlpine Young Women's Breast Cancer Study"
-The role of the tumour supressor gene TP53 in breast cancer
-Analysis of cancer registry data

Dr. Lasham and her Team became interested in leveraging spatial transcriptomics to study breast tumours in young women; breast tumours are well known for having a high degree of both intertumoural and intratumoural heterogeneity. Therefore, performing traditional bulk RNA sequencing, which provides only an aggregation of gene expression across all cells in the tumor sample, is of limited value. Dr. Lasham landed on using Stereo-seqᵀᴹ (STOmics) because of its advantage with providing unbiased detection of the whole transcriptome at single cell resolution, enabling both centimeter-level panoramic field of view and subcellular resolution of gene expression in tissues. Via Decode Science, this led her to the SAGC, which through the acquisition of the DNBSEQ-T7 sequencer from MGI, became the first Genomics Core in Australia and New Zealand to offer STOmics at scale.

The experiment presented some challenges both in terms of scale and logistics, requiring an expert pathology team to perform the breast tumour sectioning in NZ and then shipping tissue-mounted slides to the SAGC for processing and sequencing.

The STOmics technology requires mounting tissue to specialised slides with nanoscale patterned grids of barcoded probes that capture mRNA and transfer information about location when reverse transcribed. Frozen tissue mounted slides can be safely shipped and processed, but time is key, as they need to be processed within 4 weeks before the RNA quality starts to be compromised.

“Our large spatial omics experiment had plenty of moving parts; the SAGC Team was able to handle the complexities to process and deliver our results on time.”

Overall, the team processed and sequenced 3 batches of STOmics slides from Dr. Lasham’s team. Each tissue sample required a tremendous amount of sequencing coverage (1 billion reads) per 1 cm² of tissue. For analysis, the SAGC bioinformatics team provided their support using SAW (Stereo-seq Analysis Workflow) that maps sequenced reads to their spatial location on the tissue section, quantifies gene expression and combines microscope images to overlay the data to generate interactive visualisations as part of the standard pipeline.

Cutting edge technology such as STOmics has the power to transform the understanding of fundamental processes in cancer, and thus diagnosis, treatment and management of the disease. The SAGC is excited by the potential insights Dr Lasham and her team will gain from these studies and is looking forward to working with them on future projects.