Using spatial evolutionary maps to identify high-risk features of lobular carcinoma in-situ

Principal Investigator: Lucy Yates, Wellcome Sanger Institute
Funded by: CRUK Cambridge Centre Early Detection Programme Pump Priming Awards 2020

Lobular Carcinoma In-Situ (LCIS) has long been regarded as a ‘risk factor’ but not direct precursor of future invasive cancer. Reflecting this belief, clinical management of LCIS is focused on eliminating co-existent invasive disease. This has not changed, despite recent genomic analyses confirming that LCIS is actually a non-obligate precursor of Invasive Lobular Carcinoma (ILC), the second most common type of breast cancer. Differentiating between LCIS lesions that are destined to progress and those that will run an indolent course provides an opportunity for detecting and preventing breast cancer development at a very early stage.

In this project we will deepen our understanding of LCIS evolutionary biology with the ultimate goal of identifying biomarkers of future invasive disease. We will do so by using a novel spatial sequencing methodology that allows the individual subclones of a cancer to be mapped to the tissue section, permitting contextual analysis. The approach will be extremely useful for studying the wide-range of cancers that arise from precursor lesions and therefore lend themselves to early detection strategies.