The gains and losses of DNA that emerge as a consequence of mitotic errors and chromosomal instability are prevalent in cancer. These copy number alterations contribute to cancer initiaition, progression and therapeutic resistance. Here, we present a conceptual framework for examining the patterns of copy number alterations in human cancer using whole-genome sequencing, whole-exome sequencing, and SNP6 microarray data making it widely applicable to diverse datasets. Deploying this framework to 9,873 cancers representing 33 human cancer types from the TCGA project revealed a set of 19 copy number signatures that explain the copy number patterns of 93% of TCGA samples. 15 copy number signatures were attributed to biological processes of whole-genome doubling, aneuploidy, loss of heterozygosity, homologous recombination deficiency, and chromothripsis. The aetiology of four copy number signatures are unexplained and some cancer types have unique patterns of amplicon signatures associated with extrachromosomal DNA, disease-specific survival, and gains of proto-oncogenes such as MDM2. In contrast to base-scale mutational signatures, no copy number signature associated with known cancer risk factors. The results provide a foundation for exploring patterns of copy number changes in cancer genomes and synthesise the global landscape of copy number alterations in human cancer by revealing a diversity of mutational processes giving rise to copy number changes.

When considering rheumatoid arthritis (RA)-associated pulmonary diseases, interstitial lung disease and pleural disease are the most common RA-associated pulmonary manifestations while spontaneous pneumothorax and bronchopleural fistula (BPF) are among the extremely rare ones. To the best of our knowledge, all the previous reports of RA-associated BPFs were attributed to peripherally located pulmonary nodules that necrotized, burst into the pleural cavity, and eventually lead to the fistula formation. However, we hereby present the first case of BPF in an RA patient that formed in the absence of any underlying rheumatic pulmonary nodules. Additionally, our patient was on chronic methotrexate therapy, and there are no data in the literature that suggest methotrexate-induced parenchymal lung disease can predispose to BPF formation. Our report is the first to introduce a probe to further investigate this association.

A 46 YO female with PMH of DM2, HTN, Morbid obesity presented to hospital with chief complaint of chest pain, fever and SOB. She had recent hospitalization and was managed for abdominal wall abscess, MRSA bacteremia and diagnosed with infective endocarditis with aortic valve vegetation by TEE, and was discharged with antibiotics. With her current presentation: Temp was 100.8F, blood cultures grew Klebsiella Oxycota, and on TTE there was concern of increased size of aortic valve vegetation with super infection. Repeat TEE showed increase in size of vegetation. CT surgeon suggested AVR with mechanical valve. Biopsy results of the aortic valve came back as Lipomatous hamartoma. Patient recovered well post procedure and antibiotics were discontinued. Discussion: Prevalence of valvular hamartoma is as rare as 0.01 to 0.02% contributing to low diagnosis rates. If patient does not have symptoms of inflammation or infection and does not meet clinical diagnostic criteria, tumors should be included in the differential as medical management is not appropriate for hamartomas and other valvular tumors, which needs urgent surgery to prevent life threatening embolization. Cardiac valve lipomatous hamartomas are very rare lesions with preferential localization on the pericardium followed by endocardial surface. Most common histologic type of cardiac valve tumor is papillary fibroelastoma, myxoma, fibroma and hamartoma. Even if they are asymptomatic, surgical treatment should be considered to prevent embolization to brain and coronary circulation. To the best of our knowledge, we are reporting the second case of native aortic valve hamartoma so far.