Abstract. 1. The harlequin ladybird, Harmonia axyridis, is an invasive alien species that arrived in Britain in 2003 and has spread across most of the country.2. This spread has been accompanied by a decline in some native coccinellid species, in particular, the two spot ladybird Adalia bipunctata and the ten spot ladybird Adalia decempunctata. One reason for this decline could be intraguild predation (IGP) of the Adalia species by H. axyridis.3. A DNA-based approach was used to look for evidence of coccinellid IGP in the wild. Adalia bipunctata-and A. decempunctata-specific Polymerase chain reaction primers were developed to analyse the gut contents of field collected H. axyridis larvae for the presence of Adalia DNA. Harmonia axyridis larvae (156) were collected from lime trees at four sites in eastern England over 3 years.4. Adalia bipunctata DNA was detected in 7.7% and A. decempunctata DNA in 4.5% of H. axyridis larvae. DNA from both Adalia species was detected in two larvae.5. This is the first demonstration of specific IGP interactions between H. axyridis and other coccinellid species in wild populations in Britain.

Background Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally. Methods Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value. Results Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36). Conclusion Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.

In a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS‐HGNET‐MN1 cases. Whole genome sequencing however identified a novel MN1‐GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1‐PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours.

Malignant peripheral nerve sheath tumor is a rare malignancy, accounting for 3% to 10% of all soft-tissue sarcomas. We describe a previously healthy 48-year-old man who was diagnosed as having a high-grade malignant neoplasm involving the facial nerve in the right petrous canal after a 4-year history of deafness. The tumor was resected; histologic appearance and immunophenotype, including patchy but strong positivity for S100 protein, indicated a diagnosis of malignant peripheral nerve sheath tumor. A PTEN mutation, c.1003C>T p.(Arg335Ter), was subsequently identified as the cause of Cowden syndrome in another family member (a nephew) with dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), and genetic testing in the proband's daughter indicated that he was an obligate carrier of the mutation. Sequencing of the tumor showed homozygosity for c.1003C>T, confirming the presence of a germline mutation and implying loss of the second allele. With the exception of Lhermitte-Duclos disease, tumors of the nervous system are not a prominent feature of Cowden syndrome, and this is the first report of malignant peripheral nerve sheath tumor in Cowden syndrome. Sequencing results in the tumor lend evidence to PTEN gene inactivation being implicated in tumorigenesis in this case, suggesting causality rather than chance association.

Albright Hereditary Osteodystrophy (AHO) is a complex disorder defined by the presence of a short adult stature relative to the height of an unaffected parent and brachydactyly type E, as well as a stocky build, round face, and ectopic calcifications. AHO and pseudohypoparathyroidism (PHP) have been used interchangeably in the past. The term PHP describes end-organ resistance to parathyroid hormone (PTH), occurring with or without the physical features of AHO. Conversely, pseudopseudohypoparathyroidism (PPHP) describes individuals with AHO features in the absence of PTH resistance. PHP and PPHP are aetiologically linked and caused by genetic and/or epigenetic alterations in the guanine nucleotide-binding protein alpha-stimulating (G s α) locus (GNAS) in chromosome 20q13. Another less-recognised group of skeletal dysplasias, termed acrodysostosis, partially overlap with skeletal, endocrine, and neurodevelopmental features of AHO/PHP and can be overlooked in clinical practice, causing confusion in the literature. Acrodysostosis is caused by defects in two genes, PRKAR1A and PDE4D, both encoding important components of the G s α-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signalling pathway. We describe the clinical course and genotype of two adult patients with overlapping AHO features who harboured novel pathogenic variants in GNAS (c.2273C>G, p.Pro758Arg, NM_080425.2) and PRKAR1A (c.803C>T, p.Ala268Val, NM_002734.4), respectively. We highlight the value of expert radiological opinion and molecular testing in establishing correct diagnoses and discuss phenotypic features of our patients, including the first description of subcutaneous ossification and spina bifida occulta in PRKAR1A-related acrodysostosis, in the context of the novel inactivating PTH/PTH related peptide (PTHrP) signalling disorder (iPPSD) classification system.