A5016289855- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Clinical Nutrition and Gastroenterology
- Nutrition and Health in Aging
- Neurofibromatosis and Schwannoma Cases
- Renal cell carcinoma treatment
- Genomic variations and chromosomal abnormalities
- Meningioma and schwannoma management
- DNA Repair Mechanisms
- Sarcoma Diagnosis and Treatment
- Nutrition, Genetics, and Disease
- Esophageal Cancer Research and Treatment
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Renal and related cancers
- Cardiac, Anesthesia and Surgical Outcomes
- Ethics in Clinical Research
- Abdominal Surgery and Complications
- Vascular Malformations Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Congenital Ear and Nasal Anomalies
- Primary Care and Health Outcomes
- Head and Neck Anomalies
- Delphi Technique in Research
- Renal function and acid-base balance
Manchester University NHS Foundation Trust
2021-2025
Manchester University
2020-2024
University of Manchester
2019-2024
St Mary's Hospital
2019-2023
Northern Health and Social Care Trust
2023
University of Salford
2023
Manchester Academic Health Science Centre
2020-2023
Salford Royal Hospital
2022
St Mary's Hospital
2022
St. Mary's Hospital
2022
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome characterised by to cutaneous uterine leiomyomata carcinoma (RCC). To define the clinical findings, molecular genetics, prognosis in cohort of 69 families with fumarate hydratase (FH) pathogenic variant and/or features HLRCC. Clinical findings were obtained for 185 individuals from four UK regional genetics clinics. Ages at confirmed diagnoses, last dates follow-up, results attained probands...
Abstract Background Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation NF2-related schwannomatosis patients associated with increased rates subsequent (M)/malignant progression (MP). Methods All UK NF2 were eligible if they had a clinical/molecular diagnosis. Cases treated for tumors. Controls matched...
Objectives New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated accordance with these, an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted genetic counselling). The distribution variant types among and familial cases also assessed. Methods National database identifies patients meeting from a highly ascertained population cared by England’s specialised service. Diagnostic assessed 1 February 2023....
An 11-year-old presented with bilateral renal cell carcinoma (RCC) FH-deficient RCC confirmed by immunohistochemistry. WGS no coding variants but identified a rare intronic variant in FH (c.1391-269A>G). We illustrate how combined pathological and genomic investigations enabled precise diagnosis of the underlying cause an ultra-rare clinical presentation.
Abstract Breast cancer is a heterogeneous disease, at both an inter- and intra-tumoural level. Appreciating heterogeneity through the application of biomarkers molecular signatures adds complexity to tumour taxonomy but key personalising diagnosis, treatment prognosis. The extent which exists its interpretation remains challenge pathologists. Using HER2 as exemplar, we have developed simple reproducible index. Cell-to-cell was extensive in proportion reported ‘amplified’ ‘non-amplified’...
Abstract Background Limited data exist on the disease course of neurofibromatosis type 2 (NF2) to guide clinical trial design. Methods A prospective database patients meeting NF2 diagnostic criteria, reviewed between 1990 and 2020, was evaluated. Follow-up first vestibular schwannoma (VS) intervention death assessed by univariate analysis stratified age at onset, era referred, inheritance type. Interventions for NF2-related tumors were assessed. Cox regression performed determine...
Abstract In the 33 years since first diagnostic cancer predisposition gene (CPG) tests in Manchester Centre for Genomic Medicine, there has been substantial changes identification of index cases and cascade testing at-risk family members. National guidelines England Wales are usually determined from Institute healthcare Evidence these have impacted on thresholds BRCA1/2 Hereditary Breast Ovarian Cancer (HBOC) determining that all colorectal endometrial should undergo screening Lynch...
The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the bilateral oophorectomy and other breast cancer-specific survival among germline mutation. identified 664 women stage I–III cancer by combining five different datasets (retrospective prospective). Subjects were followed for 7.2 years from diagnosis death cancer. Tumour characteristics patient-reported derived medical records. Predictors determined using Cox...
Abstract Introduction Almost 60% of elderly care in‐patients are at risk malnutrition. Malnourished patients have poorer clinical outcomes and this is a key factor with respect to prolonging the length stay. Since 2003, M alnutrition U niversal S creening T ool ( MUST ) has been advocated as method for identifying these at‐risk patients. Screening should take place on admission; however, rust set stretch target aiming document score accurately within 6 h admission. Methods Three ‘care...
To assess the contribution of germline pathogenic variants (PVs) in population-based series breast cancers and best strategy to improve detection rates.
To investigate the contribution of PALB2 pathogenic gene variants (PGVs, PALB2_PGV) and CHEK2 c.1100delC (CHEK2_1100delC) PGV to familial breast ovarian cancer, PALB2_PGV associated cancer pathology.Outcomes germline CHEK2_1100delC testing were recorded in 3,127 women with histologically confirmed diagnoses invasive carcinoma situ, or epithelial nonmucinous 1,567 female controls. Breast pathology was cases from extended families.Thirty-five 44 PGVs detected patients (odds ratio [OR]...
To investigate the frequency of germline pathogenic variants (PVs) in women with bilateral breast cancer.We undertook BRCA1/2 and CHEK2 c.1100delC molecular analysis 764 samples a multigene panel 156. Detection rates were assessed by age at first primary, Manchester Score, pathology. Oestrogen receptor (ER) status contralateral versus cancer was compared on 1081 patients BRCA1/BRCA2 PVs.764 have undergone testing CHEK2; 407 also tested for PALB2 177 ATM. BRCA1 11.6%, BRCA2 14.0%, 2.4%, 1.0%,...
Background Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high moderate risk gene pathogenic variants (PVs) than female cancer, particularly BRCA2 . However, most studies only report overall detection rates without assessing detailed family history. Methods We reviewed germline testing 204 families including at least one MBC for BRCA1 , CHEK2 c.1100DelC an extended panel 93 these families. Individuals had (n=118), (FBC)(n=80),...
Abstract Individuals with the three base pair deletion NM_000267.3(NF1):c.2970_2972del p.(Met992del) have been recognised to present a milder neurofibromatosis type 1 (NF1) phenotype characterised by café-au-lait macules (CALs) and intertriginous freckling, as well lack of cutaneous, subcutaneous plexiform neurofibromas other NF1-associated complications. Examining large cohorts patients over time this specific genotype is important confirm presentation associated risks variant across...
Abstract Background Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis surveillance. However, there limited information on “real world” management VHL disease. Methods A national audit in United Kingdom. Results was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over study period, 19 genetic centres saw 842...
Background The identification of germline pathogenic gene variants (PGVs) in triple negative breast cancer (TNBC) is important to inform further primary risk reduction and TNBC treatment strategies. We therefore investigated the contribution associated PGVs familial isolated invasive TNBC. Methods Outcomes BRCA1 , BRCA2 CHEK2 _c.1100delC testing were recorded 1514 women (743—isolated, 771—familial), for PALB2 846 (541—isolated, 305—familial), with smaller numbers additional genes. Breast...
1517 Background: Li-Fraumeni syndrome (LFS) is a cancer predisposition associated with germline mutation in the TP53 tumor suppressor gene. As result of increased awareness and surveillance imaging, more asymptomatic low-grade brain lesions are being identified, raising important questions regarding management those patients. Sporadic gliomas (LGG) pediatric age rarely transform to malignant lesions, whereas prognosis high-grade (HGG) grim all groups. Although HGG hallmark LFS, little known...
To investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma situ (DCIS) and grade 1 invasive breast cancer (G1BC).We undertook BRCA1/2 analysis 311 DCIS 392 G1BC extended panel testing (non-BRCA1/2) 176/311 156/392 G1BC. We investigated PV detection by age at diagnosis, Manchester Score (MS), receptor status.30/311 (9.6%) 16/392 (4.1%) had a (p=0.003), 24/176-(13.6%) 7/156-(4.5%), respectively, non-BRCA1/2 (p=0.004). Increasing MS was associated increased...
Genetic testing for
Congenital ear anomalies and hearing impairment are often present in patients with underlying genetic disorders. Germline genomic variants responsible for at least 50% of congenital and/or childhood-onset sensorineural loss (SNHL). Furthermore, 20%–60% bilateral microtia aural atresia may have an identifiable syndrome.1 Standard diagnostic approaches involving single gene testing chromosomal microarrays limited utility diagnosing monogenic conditions high degrees phenotypic heterogeneity.2...
Background:The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity studies assessing breast risk after ovarian diagnosis.Methods:We reviewed the history in 895 PV heterozygotes (BRCA1=541).Cumulative annual incidence was assessed at 2,5,10 and >10 years following diagnosis date.Results:Breast rates were evaluated 701 assessable women with no (BRCA1=425).Incidence lower 2years (1.18%) 2-5years (1.13%),...