Alison Berner

• Master of Science
• Fellow at Barts Cancer Institute

PISCA, originally introduced by Martinez et al. in 2018, represents a pivotal Bayesian phylogenetics tool for the modeling of tumor evolution using multi-region somatic chromosomal alteration (SCA) data. PISCA takes allele-specific copy number data, typically obtained from deep genome sequencing or SNP arrays, or absolute copy number data from low-...

A major challenge for inhibiting metastasis is the ability of cancer cells to reversibly switch states in response to microenvironmental cues along the metastatic cascade. The regulatory factors and signals from the microenvironment enabling colorectal cancer (CRC) cells to transition into an invasive state and to establish metastasis in the liver...

As the rate of people openly identifying as transgender or gender diverse (TGD) is increasing, UK cancer genetics services are seeing growing numbers of TGD patients. Lack of appropriate clinical guidelines and a scarcity of robust data about the impact of gender-affirming treatments on cancer risk has led to uncertainty of how best to support TGD...

Here we tracked T cell dynamics in 15 metastatic colorectal cancer (mCRC) patients who had multiple resections (median: 3, range: 2-7) over a period of >7 years (median: 10 years, range: 7-16 years), using a novel T cell receptor sequencing (TCRseq) method. These samples had been previously characterized for DNA and methylation alterations and gene...

Introduction: Locally advanced esophageal adenocarcinoma (EAC) remains difficult to treat, and resistance is common. The ecological and evolutionary dynamics responsible for treatment failure are incompletely understood. Aim & Methods: We performed a multi-omic study with a multi-timepoint strategy to examine neoadjuvant treatment response at clona...

Locally advanced oesophageal adenocarcinoma (EAC) remains difficult to treat because of common resistance to neoadjuvant therapy and high recurrence rates. The ecological and evolutionary dynamics responsible for treatment failure are incompletely understood. Here, we performed a comprehensive multi-omic analysis of samples collected from EAC patie...

Colorectal malignancies are a leading cause of cancer-related death¹ and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4–7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of ind...

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity¹. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evoluti...

Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated ‘flip–flops’ between methylated and unmethylated states. We identify end...

Currently, most advances in site-specific epigenetic editing for human use are concentrated in basic research, yet, there is considerable interest to translate this technology beyond the bench. This review highlights recent developments with epigenetic editing technology in comparison with the canonical CRISPR-Cas genome editing, as well as the epi...

Epigenetics – the study of mechanisms that influence and modify gene expression – is providing unique insights into how an individual’s social and physical environment impact the body at a molecular level, particularly in populations that experience stigmatization and trauma. Researchers are employing epigenetic studies to illuminate how epigenetic...

Purpose of Review To best support all patients with inherited cancer risk, we must broaden our scope of practice to consider the needs of the transgender and gender diverse (trans) community. We considered best practice for supporting trans patients including tailored risk assessments and management recommendations. Recent Findings There is limite...

Colorectal malignancies are a leading cause of cancer death. Despite large-scale genomic efforts, DNA mutations do not fully explain malignant evolution. Here we study the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,373 samples from...

Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, the extent to which phenotypic variation within a tumour is a consequence of intra-tumour genetic heterogeneity remains undetermined. Here we show that colorectal cancer cells frequently have highly plastic phenotypic traits in vivo in patient tumours....

Molecular clocks record cellular ancestry. However, currently used clocks 'tick too slowly' to measure the short-timescale dynamics of cellular renewal in adult tissues. Here we develop 'rapidly oscillating DNA methylation clocks' where ongoing (de)methylation causes the clock to 'tick-tock' back-and-forth between methylated and unmethylated states...

Background Transgender men and non-binary people assigned female at birth (TMNB) who have not had surgery to remove the cervix are recommended to undertake cervical screening with the same frequency as cisgender women, but evidence suggests that TMNB have lower odds of lifetime and up-to-date cervical screening uptake. Aim To understand the attitu...

In order to adequately treat and care for patients in a holistic manner, we need to understand what influences outcome beyond disease biology. The differential impact of COVID-19 on Black and ethnic minority communities has highlighted this again, but other minority groups experience health inequalities and have unique healthcare needs. Members of...

Introduction: Over one million people in the UK identify as LGBTQ+ (lesbian, gay, bisexual, transgender, queer or questioning). Research has shown that this population experience differing cancer risk factors compared with non-LGBTQ+ patients and persistent inequalities in cancer care. Literature concerning the knowledge of oncologists of this gro...

Aneuploidy, defined as the loss and gain of whole and part chromosomes, is a near-ubiquitous feature of cancer genomes, is prognostic, and likely an important determinant of cancer cell biology. In colorectal cancer (CRC), aneuploidy is found in virtually all tumours, including precursor adenomas. However, the temporal evolutionary dynamics that se...

Cervical cancer mortality in the United Kingdom (UK) has decreased over the last decade, largely due to uptake of cervical cancer screening. However, only those with a female gender marker on their health records are invited, creating a significant barrier to gender minorities accessing screening. We undertook a systematic review to synthesise publ...

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few re...

Neuroendocrine neoplasms (NENs) arise from cells of neuronal and endocrine differentiation. Whilst they are a rare entity, an increasing proportion of patients with NEN present with metastatic disease and no evident primary site using routine imaging or histopathology. NENs of unknown primary site have a poorer prognosis, often due to the challenge...

Over the past decade, researchers in epigenetics have developed testing methods to predict the chronological and biological age of individuals based on levels of DNA methylation at combinations of CpG sites in specific cell types. These epigenetic age and aging estimators, also referred to as 'epigenetic clocks', represent a promising avenue to bet...

Powerful new genomic technologies are transforming healthcare. The faster, cheaper generation of genomic data is driving the integration of genomics into all healthcare specialties. Within the next decade, healthcare professionals will be using genomic data to diagnose and manage their patients.However, despite these exciting advances, few clinicia...

Purpose of Review We discuss the current state of genomic testing for cancer in the UK, how this has been impacted by whole genome sequencing (WGS) and the 100,000 Genomes Project, along with approaches to reviewing whole genome analyses. Recent Findings The 100,000 Genomes Project has led to the development of new pathways for tissue handling and...

Neuroendocrine neoplasms are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1-3% of all neoplasms developing in the pancreas. Despite having a low background mutation rate, driver mutations in...

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few re...

Background: Molecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be address...

Molecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be addressed. Defined...

377 Background: The effect of prior immune checkpoint inhibition therapy (CI) on the efficacy of subsequent chemotherapy is largely unknown in MUB. The identification of the optimal sequence of chemotherapy and IO is yet to be determined, but may influence outcomes. Methods: A retrospective audit and comparison of patients who progressed after firs...

Neurological conditions present a challenge when obtaining consent for lumbar punctures (LPs), as patients often have ­visual, hearing or cognitive impairments. The aim of this ­project was to improve the quality of the consent process for LPs. Surveys of doctors and patients suggested there was scope to standardise and improve information provided...

Objective: The aim of the study was to evaluate the accuracy of the sequential multiphase and dual-tracer (SMADT) technique utilizing technetium-99m pertechnetate (99mTcO4) and dynamic technetium-99m-2-methoxyisobutylisonitrile (99mTc-MIBI) with single-photon emission computed tomography/computed tomography (SPECT/CT) for localization of hyperfunc...

A 74-year-old woman presenting with acute abdominal pain underwent surgery for suspected small bowel ischaemia. At laparotomy, a sacrocolpopexy mesh in the pelvis, which had been inserted 8 years previously, was found to be causing strangulation of a 2-m length of the small bowel. Following resection and primary anastomosis, the patient spent sever...