Li-Fraumeni syndrome (LFS) is a complex hereditary cancer predisposition disorder associated with early-onset cancers in diverse tissues of origin. Germline mutations are identified in 75% of patients with classic LFS. The lifetime likelihood of a mutation carrier developing cancer approaches 75% in males and almost 100% in females. Several genetic modifiers have been implicated to account for the phenotypic variability within and across LFS families; however, efforts to develop predictive algorithms of age of onset and type of cancers in individual patients have not yet found clinical use. Although it is not possible to prevent cancers from forming in LFS patients, novel protocols have been developed for surveillance for early tumor detection, leading to improvements in survival. Comprehensive studies of the genome and epigenome in LFS families in the context of germline mutations is anticipated to shed light on this intriguing, yet devastating, disease and to transform the clinical management of patients.

Background Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child’s brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs. Methods We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany. Results Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53 . CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 ( TP53- wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1 , PER2 , and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. Conclusions We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management. Electronic supplementary material The online version of this article (10.1186/s13148-019-0708-z) contains supplementary material, which is available to authorized users.

Squamous metaplasia of the pleura with malignant transformation was observed five months after the development of an empyema and bronchopleural fistula in a 58 year old woman with lingular bronchiectasis.Squamous metaplasia of serosal surfaces, and in particular of the pleura, is uncommon.' Metaplasia progressing to carcinoma is even less common-in fact only one report (of six cases) has been published in recent years. Case reportA 58 year old woman was admitted in January 1986 with a tender subcutaneous swelling 7 cm in diameter overlying the fifth and sixth ribs in the left anterior axillary line. Some 35 years previously a bronchiectatic left lower lobe had been resected, and since then there had been occasional episodes of cough with white or green sputum. These episodes had become increasingly frequent in the previous four years, but had responded well to antibiotics. Haemoptysis had occurred twice in the six months before admission. She had had a vagotomy and pyloroplasty for duodenal ulcer in 1977, and a hysterectomy and salpingo-oophorectomy for uterine and ovarian fibroids in 1983. Laboratory investigations showed no abnormality apart from a raised erythrocyte sedimentation rate (78 mm in one hour).At operation the mass proved to be an abscess, which was treated by drainage and resection of the underlying rib. Proteus and Streptococcus species were cultured, and a postoperative sinogram and bronchogram showed a bronchopleural fistula communicating with the abscess site, plus bronchiectasis in the lingula. There was no improvement with antibiotics and physiotherapy, and after five months an empyema was decorticated and the lingula resected. Two weeks later the patient died of secondary haemorrhage from the pleural surface. Permission for a necropsy was refused.The excised lingula was bronchiectatic on gross examination, with pleural adhesions and obvious inflammation of the parenchyma. Microscopically there was severe bronchiectasis and chronic pneumonitis, with irregular fibrosis of the lung parenchyma. The pleura was thickened and densely fibrotic with foci of chronic inflammation; it was lined by moderately hyperplastic and keratotic squamous epithelium showing a prominent granular cell layer (fig 1). In large areas Address for reprint requests: Mr I M Mitchell,

Germline polymorphic variants in cancer predisposition genes such as TP53 have been shown to impact the risk of premenopausal cancer. Accordingly, the aim of this study was to assess the spectrum of polymorphisms in TP53 and its negative regulatory gene, MDM2 (SNP309:T>G) in patients with premenopausal breast cancer. Our findings in a cohort of 40 female patients demonstrate no significant correlation between the studied polymorphisms and risk of premenopausal breast cancer. Although one polymorphism is found in high frequency in this cohort (rs1800372:A>G, 9.0%), it was not associated with the risk of developing cancer before the age of 35 years in an extended cohort of 1,420 breast cancer cases. Functional studies of the rs1800372:A>G polymorphic allele reveal that it does not affect p53 transactivation function. Further study of variants or mutations in other cancer susceptibility genes is warranted to refine our understanding of the germline contribution to premenopausal breast cancer susceptibility.

After publication of the original article [1], authors have requested to add a ‘J’ as middle name for Richard Gilbertson. Hence, full name should be Richard J Gilbertson.

Liquid biopsy, specifically circulating tumor DNA (ctDNA) detection, has started to revolutionize the clinical management of patients with cancer by surpassing many limitations of traditional tissue biopsies, particularly for serial testing. ctDNA sequencing has been successfully utilized for cancer detection, prognostication, and assessment of disease response and evolution. While the applications of ctDNA analysis are growing, the majority of studies to date have primarily evaluated its use as a tool for tracking a known cancer, and in most cases at advanced stage. Herein, we discuss the potential application of ctDNA for surveillance and early cancer detection in patients with a cancer predisposition syndrome.

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Tumours arising in the chemoreceptor system are termed chemodectomas. Intrathoracic chemodectoma is a rare tumour, only 74 Case reportA 38-year-old housewife was referred to the cardiac unit for investigation of hypertension which had persisted since her first pregnancy three years previously. She was a non-smoker and was not taking the contraceptive pill. At presentation the blood pressure was 160/110 mm Hg. There was no radiofemoral delay or renal bruits and both optic fundi were normal. The chest radiograph and tomograms showed a lobulated mass in the paravertebral region at the level of T6/T7 (fig 1 a, b) which appeared highly vascular at aortography. Computerised axial tomography was performed to define the relationship to the vertebral bodies, and this revealed that the mass entered the body of the vertebra of T6 (fig 2). Two 24-hour urine collections were analysed for urinary catecholamines and showed grossly raised normetadrenaline (NMA): 3323 ,ug/24 hours and 2802 gg/24 hours (NR: 204-585). Urine homovanillic acid (HVA) and metadrenaline (MA) excretions were normal.Operation was performed and the arterial pressure and ECG were monitored continuously. Blood pressure was controlled by an intravenous infusion of phentolamine 1 mg/ml at 3 mg/min, supplemented by intravenous boluses of 2 mg propranolol, especially when the tumour was being manipulated. After removal of the tumour there was a fall of the systolic blood pressure to 80 mm Hg which responded to blood transfusion, and thereafter the blood pressure remained stable.