Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.
SUMMARY We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.
Based on high quality surgery and scientific data, scientists and surgeons are committed to protecting patients as well as healthcare staff and hereby provide this Guidance to address the special issues circumstances related to the exponential spread of the Coronavirus disease 2019 (COVID-19) during this pandemic. As a basis, the authors used the British Intercollegiate General Surgery Guidance as well as recommendations from the USA, Asia, and Italy. The aim is to take responsibility and to provide guidance for surgery during the COVID-19 crisis in a simplified way addressing the practice of surgery, healthcare staff and patient safety and care. It is the responsibility of scientists and the surgical team to specify what is needed for the protection of patients and the affiliated healthcare team. During crises, such as the COVID-19 pandemic, the responsibility and duty to provide the necessary resources such as filters, Personal Protective Equipment (PPE) consisting of gloves, fluid resistant (Type IIR) surgical face masks (FRSM), filtering face pieces, class 3 (FFP3 masks), face shields and gowns (plastic ponchos), is typically left up to the hospital administration and government. Various scientists and clinicians from disparate specialties provided a Pandemic Surgery Guidance for surgical procedures by distinct surgical disciplines such as numerous cancer surgery disciplines, cardiothoracic surgery, ENT, eye, dermatology, emergency, endocrine surgery, general surgery, gynecology, neurosurgery, orthopedics, pediatric surgery, reconstructive and plastic surgery, surgical critical care, transplantation surgery, trauma surgery and urology, performing different surgeries, as well as laparoscopy, thoracoscopy and endoscopy. Any suggestions and corrections from colleagues will be very welcome as we are all involved and locked in a rapidly evolving process on increasing COVID-19 knowledge.
The article presents a case report of a patient with an intramural gastric hematoma. Diagnostic examinations were suggestive of a suspected gastrointestinal stromal tumor Normal image was observed in gastroscopic examination while abdominal CT scan revealed a nodular lesion along the greater curvature of the stomach extending from the posterior wall and adjoining the pancreas and the spleen. The patient was qualified for surgical treatment. Laparotomy was performed followed by total gastric resection and Roux-en-Y reconstruction of the gastrointestinal tract. Post-operative histopathological examination revealed the presence of an extensive hematoma penetrating the perigastric fat tissue along with numerous hemosiderinophages and segmental indicators of formation of inflammatory granulation tissue suggestive of a chronic nature of the lesion. Immunohistochemical GIST assays (CD117, DOG-1, CD34, CD31, SMA, S-100, CKAE1/AE3, Ki-67) were negative. No complications were observed in the post-operative course. Patient is subject to continued follow-up and observation. Follow-up gastroscopy and abdominal CT scan performed 6 months after the surgery revealed an unremarkable image.
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