Next generation mapping reveals novel large genomic rearrangements in prostate cancer

Complex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new technology that allows for the interrogation of megabase length DNA molecules outside the detection range of single-base resolution NGS. In this study, we sought to determine the feasibility of using the Irys (Bionano Genomics Inc.) nanochannel NGM technology to generate whole genome maps of a primary prostate tumor and matched blood from a Gleason score 7 (4 + 3), ETS-fusion negative prostate cancer patient. With an effective mapped coverage of 35X and sequence coverage of 60X, and an estimated 43% tumor purity, we identified 85 large somatic structural rearrangements and 6,172 smaller somatic variants, respectively. The vast majority of the large SVs (89%), of which 73% are insertions, were not detectable ab initio using high-coverage short-read NGS. However, guided manual inspection of single NGS reads and de novo assembled scaffolds of NGM-derived candidate regions allowed for confirmation of 94% of these large SVs, with over a third impacting genes with oncogenic potential. From this single-patient study, the first cancer study to integrate NGS and NGM data, we hypothesise that there exists a novel spectrum of large genomic rearrangements in prostate cancer, that these large genomic rearrangements are likely early events in tumorigenesis, and they have potential to enhance taxonomy.This work was supported by Movember Australia and the Prostate Cancer Foundation Australia (PCFA) as part of the Movember Revolutionary Team Award (MRTA) to the Garvan Institute of Medical Research program on prostate cancer bone metastasis (ProMis to P.I.C. and V.M.H.) dedicated to establishing NGM for clinically relevant prostate cancer, and the Australian Prostate Cancer Research Centre NSW (APCRC-NSW). Participant recruitment and sampling was supported by the Cancer Association of South Africa (CANSA to M.S.R.B and V.M.H.). W.J. is supported by APCRC-NSW, E.K.F.C. and D.C.P. are partly supported by ProMis, P.I.C. is supported by Mrs Janice Gibson and the Ernest Heine Family Foundation, Australia, and V.M.H. is supported by the University of Sydney Foundation and Petre Foundation, Australia.www.impactjournals.com/oncotargetam2018School of Health Systems and Public Health (SHSPH

Case of a nodular ear

Angiolymphoid hyperplasia with eosinophilia is a benign condition which presents as vascular nodules or plaques, which are often multiple and grouped, located in the head and neck region, especially around the ears. It is associated with arteriovenous shunts in many cases, and they may be painful, pruritic, or pulsatile. On histology, it is characterized by proliferation of blood vessels with epithelioid cells surrounding the larger vessels and accompanied by eosinophils. Various treatment modalities have been described. Here, we present the case of a 30-year-old female with angiomatous nodules over the left ear,which were successfully treated

Assessing the new ICD-MM classification for assigning the cause of maternal mortality at a tertiary centre in Western India: a retrospective study

Background: The World Health Organisation (WHO) in 2012 introduced the 10th revision of International Classification of Disease (ICD 10) to deaths in pregnancy, labour and puerperium (ICD-MM) for consistent collection, analysis and interpretation of information on maternal deaths. The proper use of this classification requires training to avoid heterogeneity and error in the classification of maternal deaths.Methods: We analysed the Maternal Death Review (MDR) forms of 295 deaths over a period of 5 years (January 2014 to December 2018 inclusive) occurring at a tertiary health centre in Western India. The ICD-MM classification was used to reassign the cause of death.Results: There were 295 deaths in women during pregnancy, childbirth and puerperium during the 5 year period. Of these there were 294 maternal deaths and one coincidental death. There were 173 deaths of the direct type (58.84%), 105 deaths of the indirect type (35.71%) and 16 deaths (5.44%) of the unspecified type. Obstetric haemorrhage was  the highest contributor to direct deaths (23.8%) and anaemia contributed to the maximum deaths from indirect causes (13.6%) followed by liver diseases in pregnancy (10.54%).Unanticipated complications of management accounted for 2% of the total deaths. There was considerable inaccuracy in assigning cause of death by consultants who were untrained in the use of the ICD-MM classification.Conclusions: ICD-MM classification promotes an accurate assignment of the cause of death. Training of healthcare providers performing maternal death reviews in the use of this classification is essential to identify accurate underlying cause of death and contributory conditions.

The Relationship between pH and MaSp1 Structure

Spider silk has recently developed into a worthwhile avenue of research for scientists, due in part to the versatility and industrial potential of natural silk. Because of their high tensile strength and extensibility, silk threads are considered some of the strongest biomaterials in existence, exhibiting high mechanical stability and biocompatibility. Prior experimentation concerning the N-terminal region of major ampullate spidroin 1 has shown that it plays a major role in facilitating assembly of the fiber by accelerating and directing assembly in response to the environmental pH. More importantly, the domain contains and codes for an inherent secretion signal, instructing the internal machinery of L. hesperus to transport the spidroins into the glandular lumen and begin fiber secretion. It is believed that fiber aggregation preceding extrusion can be attributed to the concentration of salts in the luminal contents of the major ampullate gland. In order to test this claim, a cDNA sequence responsible for producing MaSp1 was inserted into the plasmid vector pBAD-TOPO and digested to confirm the presence of the insert. The gene was induced in the presence of arabinose to express its MaSp1 protein. The spidroin, which was initially tagged with histidine residues to allow for isolation using a nickel resin, was size fractioned using SDS-PAGE. Finally, a silver stain was performed to allow for protein visualization and removal from the gel to perform an in-gel tryptic digest. Mass spectrometry and atomic force microscopy analysis were utilized as tools to study the relationship between protein structure and pH. The results of this study will help reveal the ideal conditions under which large-scale fiber synthesis can be made possible

The Relationship between pH and MaSp1 Structure

Spider silk has recently developed into a worthwhile avenue of research for scientists, due in part to the versatility and industrial potential of natural silk. Because of their high tensile strength and extensibility, silk threads are considered some of the strongest biomaterials in existence, exhibiting high mechanical stability and biocompatibility. Prior experimentation concerning the N-terminal region of major ampullate spidroin 1 has shown that it plays a major role in facilitating assembly of the fiber by accelerating and directing assembly in response to the environmental pH. More importantly, the domain contains and codes for an inherent secretion signal, instructing the internal machinery of L. hesperus to transport the spidroins into the glandular lumen and begin fiber secretion. It is believed that fiber aggregation preceding extrusion can be attributed to the concentration of salts in the luminal contents of the major ampullate gland. In order to test this claim, a cDNA sequence responsible for producing MaSp1 was inserted into the plasmid vector pBAD-TOPO and digested to confirm the presence of the insert. The gene was induced in the presence of arabinose to express its MaSp1 protein. The spidroin, which was initially tagged with histidine residues to allow for isolation using a nickel resin, was size fractioned using SDS-PAGE. Finally, a silver stain was performed to allow for protein visualization and removal from the gel to perform an in-gel tryptic digest. Mass spectrometry and atomic force microscopy analysis were utilized as tools to study the relationship between protein structure and pH. The results of this study will help reveal the ideal conditions under which large-scale fiber synthesis can be made possible

La Petite presse : journal quotidien... / [rédacteur en chef : Balathier Bragelonne]

21 septembre 18721872/09/21 (N2328)