Genomic profiling using the UltraSEEK panel identifies discordancy between paired primary and breast cancer brain metastases and an association with brain metastasis-free survival.

Purpose: Brain metastases (BM) are an increasing clinical problem. This study aimed to assess paired primary breast cancers (BC) and BM for aberrations within TP53, PIK3CA, ESR1, ERBB2 and AKT utilising the MassARRAY® UltraSEEK® technology (Agena Bioscience, San Diego, USA).

Methods: DNA isolated from 32 paired primary BCs and BMs was screened using the custom UltraSEEK® Breast Cancer Panel.

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review.

Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth.

The PI3K-AKT signalling cascade has a highly conserved role in a variety of processes including cell growth and glucose homoeostasis. Variants affecting this pathway can lead to one of several segmental overgrowth disorders. These conditions are genetically heterogeneous and require tailored, multidisciplinary involvement throughout life.

What do we need to make circulating tumour DNA (ctDNA) a routine diagnostic test in lung cancer?

The gold standard test for detection of epidermal growth factor receptor (EGFR) mutation is to genotype somatic DNA extracted from a tissue biopsy or cytology specimen. Yet, in at least 20% of patients this is not possible for various reasons including insufficient availability of neoplastic tissue, lack of fitness of the available tissue for a biopsy or that a biopsy is not technically feasible. Consequently, there has been intense investigation of circulating tumour DNA (ctDNA), released into the plasma fraction of blood from cancer cells during apoptosis/necrosis, as a minimally invasive 'liquid biopsy' and surrogate for cancer tissue.