Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes.

Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol.

Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer.

Background: Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection.

Methods: Defective mismatch repair (dMMR) status was determined by either loss of mismatch repair protein expression on IHC or microsatellite instability (MSI) by PCR in 127 APC biopsies from 124 patients (Royal Marsden [RMH] cohort); MSI by targeted panel next-generation sequencing (MSINGS) was then evaluated in the same cohort and in 254 APC samples from the Stand Up To Cancer/Prostate Cancer Foundation (SU2C/PCF). Whole exome sequencing (WES) data from this latter cohort were analyzed for pathogenic MMR gene variants, mutational load, and mutational signatures.

Molecular profiling of colorectal pulmonary metastases and primary tumours: implications for targeted treatment.

This study aimed to molecularly characterise colorectal pulmonary metastases (PM) and investigate whether their molecular profiles were concordant with those of the primary tumour. Clinical data and archival formalin fixed paraffin embedded tissue samples were retrospectively collected from patients who underwent ≥ 1 pulmonary metastasectomies for colorectal cancer between 1997-2012. Primary tumour and metastatic samples were analysed using a targeted capture sequencing panel of 46 cancer-associated genes.

Cyclin D1 overexpression in proliferation centres of small lymphocytic lymphoma/chronic lymphocytic leukaemia.

The recent publication reviewing the updated WHO classification commented on the presence of cyclin D1-positive cells in the proliferation centres (PC) of small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL). The figure quoted was 30%, which appeared higher than our experience. To assess cyclin D1 expression in PC of SLL/CLL cases, we performed a review of SLL/CLL cases diagnosed at the Royal Marsden Hospital between 1996 and 2009.

Marginal zone lymphoma: Associated autoimmunity and auto-immune disorders.

Large epidemiological studies have shown a consistent increased risk for developing lymphoma in the setting of autoimmune disorders (AID). It is known that this link appears to be stronger for some AID and certain non-Hodgkin lymphoma subtypes e.g.