Biology subjects

House, E.

Publications and source records attributed to House, E..

3 recordsLinked to original sources

bioRxiv2024

Predictive biomarkers of breast ductal carcinoma in situ may underestimate the risk of recurrence due to de novo ipsilateral breast carcinoma development

Development of ipsilateral breast carcinoma following diagnosis of breast ductal carcinoma in situ (DCIS) has been assumed to represent recurrence of the primary tumour. However, this may not be the case and it is important to know how often recurrences are new tumours. Ipsilateral primary-recurrence pairs (n=78) were sequenced to test their clonal relatedness. Shared genetic events were identified from whole exome sequencing (n=54 pairs) using haplotype-specific copy number and phylogenetic analysis. The remaining pairs were sequenced by a targeted panel or low-coverage whole genome sequencing. We included 32 non-recurrent DCIS to compare recurrent and non-recurrent disease. We found that 7% of DCIS recurrences were non-clonal by whole exome sequencing, indicative of a new breast carcinoma. Lower resolution methods detected a higher non-clonality rate (29%). Comparing primary DCIS with their recurrences found that evolution of DCIS to invasive disease was associated with increased ploidy and copy number events. TP53 mutations were enriched in DCIS with clonal recurrence compared with non-recurrent DCIS. Our results verify that de novo "recurrent tumours" of independent origin occur in patients who may be at high risk.

cancer biology↗

bioRxiv2022

Utility of stromal lymphocytes in diagnosis and predicting upgrade of B3 breast lesions from core biopsies

For more than two decades attempts have been made to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 lesions) who could safely be observed rather than being treated with surgical excision and/or chemoprevention. Various histopathological, clinical and imaging parameters for risk recommendation have been evaluated, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade lesion to either ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC). While on average 30% of these patients are upgraded after diagnostic biopsy, a large number are over treated,making this an important harm of screening. Here we evaluated stromal lymphocytes from B3 biopsies (n=264) as a predictive biomarker for upgrade. A higher number of stromal lymphocytes were observed in upgraded B3 lesions than non-upgraded (p< 0.01, zero inflated binomial model) for both ductal and papillary lesions (n=174). This observation was validated in an independent cohort (p<0.001, p<0.05, zero binomial model, ductal and papillary lesions, respectively) (n=90). Our data suggested that the presence of [≥]5% of lymphocytes in the surrounding specialised stroma of B3 lesions are predictive of B3 lesions being upgraded with a specificity of 93% and 87% in our discovery and validation cohorts, respectively. The area under the curve (AUC) for the discovery cohort using lymphocyte count and age as variables was 0.77 and was validated with an AUC of 0.81 in the validation cohort. In conclusion, we can identify a subset of the patients at risk of upgrade with high specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic.

cancer biology↗

bioRxiv2019

Notes on the endemic cloud forest plants of the Cameroon Highlands and the new, Endangered, Tricalysia elmar (Coffeeae-Rubiaceae)

Background and aimsThis paper reports a further discovery in the context of a long-term botanical survey in the Cross River-Sanaga interval of west-central Africa, focussing on species discovery and conservation.\n\nMethodsNormal practices of herbarium taxonomy have been applied to study the material collected. The relevant collections are stored in the Herbarium of the Royal Botanic Gardens, Kew, London and at the Institute of Research in Agronomic Development - National Herbarium of Cameroon.\n\nKey resultsNew species to science continue to be discovered from the cloud (submontane) forests of the Cameroon Highlands in Cameroon. Most of these species are rare, highly localised, and threatened by habitat destruction. These discoveries increase the justification for improved conservation management of surviving habitat. Tricalysia elmar Cheek (Coffeeae-Rubiaceae) is described as an additional species new to science and is compared with similar species of the genus. Restricted so far to four locations, Mt Kupe, Bali Ngemba, Lebialem and Nta Ali, its conservation status is assessed as Endangered (EN B1+2ab(iii)) according to the 2012 criteria of IUCN.

plant biology↗