scholarly journals Cross-species comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma

2021 ◽  
Author(s):  
Kim Wong ◽  
Latasha Ludwig ◽  
Oscar Krijgsman ◽  
David J. Adams ◽  
Geoffrey A. Wood ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Lymphatic Vessels ◽  
Cancer Genes ◽  
Driver Genes ◽  
Risk Genes ◽  
Cardiac Neoplasms ◽  
Pathogenic Variants ◽  
Aggressive Tumor ◽  
Cross Species Comparison

Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that carries a poor prognosis. The rarity of AS, together with its heterogeneous nature, and locations (skin, breast, visceral organs and deep soft tissues), makes understanding the pathogenesis of AS challenging. Dogs and cats spontaneously develop hemangiosarcoma (HSA), an aggressive tumor that shares many histopathological and clinical similarities to AS. To investigate the genetic suitability of spontaneously occurring HSA as a model for AS, we sequenced ∼1,000 cancer genes in 41 cases of HSA and matched germline tissue; 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of canine and feline HSA to human AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. In the germlines, by focusing specifically on canine and feline orthologs of human AS risk genes, we identified several candidate pathogenic variants. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs. Furthermore, both AS and canine HSA show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrate many important parallels to AS and provides hope that future studies on these cancers will benefit patients of all three species.

scholarly journals Ranking cancer drivers via betweenness-based outlier detection and random walks

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cesim Erten ◽  
Aissa Houdjedj ◽  
Hilal Kazan
Keyword(s):  
Cancer Genomics ◽  
Interaction Network ◽  
Molecular Data ◽  
Alternative Methods ◽  
Patient Specific ◽  
Cancer Genes ◽  
Driver Genes ◽  
Cancer Driver ◽  
Protein Protein Interaction ◽  
Genomic Studies

Abstract Background Recent cancer genomic studies have generated detailed molecular data on a large number of cancer patients. A key remaining problem in cancer genomics is the identification of driver genes. Results We propose BetweenNet, a computational approach that integrates genomic data with a protein-protein interaction network to identify cancer driver genes. BetweenNet utilizes a measure based on betweenness centrality on patient specific networks to identify the so-called outlier genes that correspond to dysregulated genes for each patient. Setting up the relationship between the mutated genes and the outliers through a bipartite graph, it employs a random-walk process on the graph, which provides the final prioritization of the mutated genes. We compare BetweenNet against state-of-the art cancer gene prioritization methods on lung, breast, and pan-cancer datasets. Conclusions Our evaluations show that BetweenNet is better at recovering known cancer genes based on multiple reference databases. Additionally, we show that the GO terms and the reference pathways enriched in BetweenNet ranked genes and those that are enriched in known cancer genes overlap significantly when compared to the overlaps achieved by the rankings of the alternative methods.

Design and validation of a modular micro-robotic system for the mechanical characterization of soft tissues

2021 ◽  
Author(s):  
Andrea Acuna ◽  
Julian M. Jimenez ◽  
Naomi Deneke ◽  
Sean M. Rothenberger ◽  
Sarah Libring ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Mechanical Characterization ◽  
Robotic System

scholarly journals Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Stetson Thacker ◽  
Charis Eng
Keyword(s):  
Autism Spectrum ◽  
Pten Expression ◽  
Differentially Expressed ◽  
Risk Genes ◽  
Animal Modeling ◽  
Network Analyses ◽  
Phosphorylated Proteins ◽  
Mass Spectrometry Technology ◽  
Neurological Processes

AbstractPTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential insight into ASD pathogenesis. Subsequently, we comprehensively characterized the neural (phospho)proteome of Ptenm3m4/m3m4 mice, which exhibits cytoplasmic-predominant Pten expression, by applying mass spectrometry technology to their brains at two-weeks- (P14) and six-weeks-of-age (P40). The differentially expressed/phosphorylated proteins were subjected to gene enrichment, pathway, and network analyses to assess the affected biology. We identified numerous differentially expressed/phosphorylated proteins, finding greater dysregulation at P40 consistent with prior transcriptomic data. The affected pathways were largely related to PTEN function or neurological processes, while scant direct overlap was found across datasets. Network analysis pointed to ASD risk genes like Pten and Psd-95 as major regulatory hubs, suggesting they likely contribute to initiation or maintenance of cellular and perhaps organismal phenotypes related to ASD.

scholarly journals High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

2021 ◽  
pp. jmedgenet-2020-107347
Author(s):  
D Gareth Evans ◽  
Elke Maria van Veen ◽  
Helen J Byers ◽  
Sarah J Evans ◽  
George J Burghel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Ductal Carcinoma ◽  
Cancer Genes ◽  
Early Onset Breast Cancer ◽  
Younger Women ◽  
Pathogenic Variants ◽  
Younger Age ◽  
Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Limitations of direct-to-consumer (DTC) genetic testing for hereditary breast and ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10515-10515
Author(s):  
Neelam Vijay Desai ◽  
Elizabeth Dominic Barrows ◽  
Sarah M. Nielsen ◽  
Kathryn E. Hatchell ◽  
Edward D. Esplin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Indication ◽  
Ovarian Cancer Risk ◽  
Cancer Genes ◽  
Primary Analysis ◽  
Risk Genes ◽  
Group 3 ◽  
Group 5

10515 Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant (PLPV) in BRCA1/2 or other cancer-risk genes. Methods: Multi-panel genetic testing was performed in 348,692 individuals for a clinical indication of hereditary breast/ovarian cancer (Clinical cohort) and 7,636 self-referred ostensibly healthy individuals (Healthy cohort) by a clinical testing laboratory. The primary analysis evaluated PLPVs for Group 1 genes: BRCA1/2 AJ founder variants and Group 2: full sequence BRCA1/2. Secondary analyses assessed PLPVs in Group 3: high-risk breast cancer genes ( BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53), Group 4: all breast or ovarian cancer-risk genes (Group 3 genes plus ATM, BARD1, BRIP1, truncating CHEK2, EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D) and Group 5: 41 cancer-risk genes; these analyses were limited to participants who tested for all 41 genes. Potentially mosaic variants were excluded. Results: Table illustrates PLPVs found in both cohorts. The BRCA1/2 AJ founder variants account for only ̃11% (1513/13,987) and ̃30% (19/64) of the BRCA PLPVs in the Clinical and Healthy cohorts, respectively. Even among AJ individuals, testing only for the 3 founder variants will miss ̃10% (52/513) of all BRCA1/2 PLPVs. Evaluating only the BRCA AJ founder variants missed a higher percentage of PLPVs in other cancer-risk genes. Conclusions: The 3 BRCA1/2 AJ founder variants analyzed by DTC testing account for a small fraction of PLPVs in cancer-risk genes in the general population, and miss 10% of BRCA PLPVs even among AJ individuals. Greater public education is needed to dispel the misconception that DTC tests are equivalent to clinical assessment and comprehensive genetic testing. PLPVs identified in Clinical and Healthy Cohorts.[Table: see text]

Thumb Injuries and Instabilities. Part 2: Spectrum of Lesions

2021 ◽  
Vol 25 (02) ◽  
pp. 355-365
Author(s):  
Alain G. Blum ◽  
Marnix T. van Holsbeeck ◽  
Stefano Bianchi
Keyword(s):  
Soft Tissues ◽  
Imaging Techniques ◽  
Metacarpophalangeal Joint ◽  
Resonance Imaging ◽  
Ligament Injuries ◽  
First Line ◽  
Collateral Ligament ◽  
Traumatic Injuries ◽  
Line Imaging

AbstractThe motor function of the thumb and its alignment with regard to the hand make it particularly vulnerable to trauma. Pathology encountered in this joint is varied, and imaging techniques play a crucial role in the diagnosis and characterization of injury. Despite advances in imaging technology, acute thumb injuries remain a challenge for radiologists. Currently, standard radiography and ultrasonography are frequently used first-line imaging techniques. Computed tomography is most often indicated for complex fractures and dislocations. Magnetic resonance imaging may be used to optimally characterize soft tissues and bone marrow. In this article, we cover the most common traumatic injuries: fractures, dislocations, collateral ligament injuries of the metacarpophalangeal joint, as well as soft tissue lesions.

A NEW PARAMETER ESTIMATION METHOD FOR ONLINE SOFT TISSUE CHARACTERIZATION

2016 ◽  
Vol 16 (08) ◽  
pp. 1640019 ◽  
Author(s):  
JAEHYUN SHIN ◽  
YONGMIN ZHONG ◽  
JULIAN SMITH ◽  
CHENGFAN GU
Keyword(s):  
Soft Tissue ◽  
Linear Regression ◽  
Tissue Characterization ◽  
Soft Tissues ◽  
Unscented Kalman Filter ◽  
Estimation Method ◽  
Regression Method ◽  
Linear Regression Method ◽  
Non Linear

Dynamic soft tissue characterization is of importance to robotic-assisted minimally invasive surgery. The traditional linear regression method is unsuited to handle the non-linear Hunt–Crossley (HC) model and its linearization process involves a linearization error. This paper presents a new non-linear estimation method for dynamic characterization of mechanical properties of soft tissues. In order to deal with non-linear and dynamic conditions involved in soft tissue characterization, this method improves the non-linearity and dynamics of the HC model by treating parameter [Formula: see text] as independent variable. Based on this, an unscented Kalman filter is developed for online estimation of soft tissue parameters. Simulations and comparison analysis demonstrate that the proposed method is able to estimate mechanical parameters for both homogeneous tissues and heterogeneous and multi-layer tissues, and the achieved performance is much better than that of the linear regression method.

scholarly journals Idiopathic Multifocal Osteolysis: Case of Surgical Treatment

2015 ◽  
Vol 22 (3) ◽  
pp. 78-83
Author(s):  
A. P Pozdeev ◽  
E. A Zakhar’yan ◽  
D. S Buklaev ◽  
I. N Krasnogorskiy ◽  
T. F Zubairov
Keyword(s):  
Clinical Case ◽  
Soft Tissues ◽  
Weight Bearing ◽  
Lymphatic Vessels ◽  
Bisphosphonate Therapy ◽  
Surgical Interventions ◽  
Massive Osteolysis ◽  
Thin Walls ◽  
Idiopathic Osteolysis ◽  
Tubular Bones

Idiopathic osteolysis is a rare disorder characterized by spontaneous, massive and progressive resorption of bone tissue. Massive osteolysis results from proliferation of blood and lymphatic vessels with thin walls, resembling capillaries, in the bone and surrounding soft tissues. Literature review on this problem and clinical case of a patient successfully operated on using the technique elaborated at our clinic are presented. Surgical interventions enabled to achieve the restoration of tubular bones integrity and ensured conditions for independent patient’s movement. Possibility of the performance of reconstructive surgical interventions for the restoration of limb weight bearing ability that is reasonable to combine with bisphosphonate therapy.

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