scholarly journals P53 and PIK3CA Mutations in KRAS/HER2 Negative Ovarian Intestinal-Type Mucinous Carcinoma Associated with Mature Teratoma

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Sarah Bouri ◽  
Philippe Simon ◽  
Nicky D’Haene ◽  
Xavier Catteau ◽  
Jean-Christophe Noël
Keyword(s):  
Recurrent Disease ◽  
Mature Teratoma ◽  
Mucinous Carcinoma ◽  
Intestinal Type ◽  
Molecular Profile ◽  
Pik3ca Mutations ◽  
First Case ◽  
Therapeutic Outcomes ◽  
Generation Sequencing ◽  
P53 Genes

Primary ovarian intestinal-type mucinous carcinomas associated with mature teratoma are rare and represent less than 3% of all primary ovarian neoplasms. The molecular profile of these tumors is still controversial. We report here the first case of mucinous ovarian tumor in which mutation of the PIK3CA and P53 genes could be demonstrated by the next generation sequencing technique without KRAS mutation or HER2 amplification. Our data suggest that these mucinous carcinoma variants probably present an extremely complex molecular biology profile that should be known in the future to stratify therapeutic outcomes and potential targeted therapies, particularly in recurrent disease.

scholarly journals PATH-17. NOVEL DUAL HISTONE 3 K27M AND G34R POINT MUTATIONS IN A MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii167-ii167
Author(s):  
Peter Pan ◽  
Tejus Bale ◽  
Alexandra Miller ◽  
Marc Ladanyi ◽  
Marc Rosenblum ◽  
...  
Keyword(s):  
Point Mutations ◽  
Histone 3 ◽  
First Case ◽  
Microvascular Proliferation ◽  
Motor Neuron Facial Nerve ◽  
Methylguanine Methyltransferase ◽  
Mitotic Figures ◽  
In Cis ◽  
Generation Sequencing ◽  
Diffuse Midline Glioma

Abstract BACKGROUND Histone H3 alterations due to mutations on H3F3A and HIST1H3B genes, have in recent years been associated with distinct entities and tumor locations within the context of infiltrative gliomas. H3K27M is associated with a midline location and is included in the WHO 2016 as the diffuse midline glioma H3K27M-mutant, a specific diagnostic entity. H3G34R, thought to be a mutually exclusive alteration, is less common but has been associated with a cerebral hemispheric location. We report the first case to our knowledge with both of these alterations in the same tumor. METHODS Clinical and pathologic records of the patient were reviewed and presented. RESULTS A 39-year-old man presented with acute right face, arm, and leg numbness and mild weakness; examination was notable for right lower motor neuron facial nerve palsy and numbness, along with numbness and subtle slowing of rapid alternating movements in the left arm and leg. A non-enhancing left thalamic mass was identified and stereotactically biopsied. Infiltrative glial neoplasm with moderately-increased cellularity was seen, with ovoid cells, enlarged nuclei, apoptotic bodies, and mitotic figures. No necrosis or microvascular proliferation seen. Immunostain was positive for H3K27M. O6-methylguanine-methyltransferase (MGMT) promoter was not methylated. Next-generation sequencing showed dual in cis H3 point mutations in K27M (HIST1H3B c.83A >T) and G34R (HIST1H3B c.103G >C). Additional alterations were noted in NF1, PIK3CA, ATRX, FGFR3, and NSD1. Isocitrate dehydrogenase (IDH1/2) mutations were not identified. CONCLUSION This case of a young man with a midline glioma is novel for carrying both H3K27M and H3G34R alterations and indicates these alterations are not mutually exclusive. The interaction seen here suggests H3K27M dominance for a midline phenotype.

scholarly journals Fetus in fetu: two case reports from North African country

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Moutaz Ragab ◽  
Omar Nagy Abdelhakeem ◽  
Omar Mansour ◽  
Mai Gad ◽  
Hesham Anwar Hussein
Keyword(s):  
Histopathological Examination ◽  
Case Reports ◽  
Abdominal Mass ◽  
Mature Teratoma ◽  
Surgical Techniques ◽  
Rare Condition ◽  
Mass Effect ◽  
Fetus In Fetu ◽  
Vascular Connection ◽  
First Case

Abstract Background Fetus in fetu is a rare congenital anomaly. The exact etiology is unclear; one of the mostly accepted theories is the occurrence of an embryological insult occurring in a diamniotic monochorionic twin leading to asymmetrical division of the blastocyst mass. Commonly, they present in the infancy with clinical picture related to their mass effect. About 80% of cases are in the abdomen retroperitoneally. Case presentation We present two cases of this rare condition. The first case was for a 10-year-old girl that presented with anemia and abdominal mass, while the second case was for a 4-month-old boy that was diagnosed antenatally by ultrasound. Both cases had vertebrae, recognizable fetal organs, and skin coverage. Both had a distinct sac. The second case had a vascular connection with the host arising from the superior mesenteric artery. Both cases were intra-abdominal and showed normal levels of alpha-fetoprotein. Histopathological examination revealed elements from the three germ layers without any evidence of immature cells ruling out teratoma as a differential diagnosis. Conclusions Owing to its rarity, fetus in fetu requires a high degree of suspicion and meticulous surgical techniques to avoid either injury of the adjacent vital structures or bleeding from the main blood supply connection to the host. It should be differentiated from mature teratoma.

scholarly journals Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period

2019 ◽  
Vol 8 (8) ◽  
pp. 1149-1158 ◽  
Author(s):  
Jordyn Silverstein ◽  
Wesley Kidder ◽  
Susan Fisher ◽  
Thomas A Hope ◽  
Samantha Maisel ◽  
...  
Keyword(s):  
Significant Risk ◽  
Case Series ◽  
Stage Iv ◽  
Receptor Expression ◽  
Primary Tumors ◽  
Molecular Features ◽  
First Case ◽  
Hormone Receptor Expression ◽  
Generation Sequencing ◽  
Formalin Fixed

Background Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. Methods We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. Results All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. Discussion CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

scholarly journals Distinct Genomic Landscape of Colorectal Mucinous Carcinoma Determined via Comprehensive Genomic Profiling: Steps to a New Treatment Strategy

2021 ◽  
Vol 11 ◽  
Author(s):  
Liang Huang ◽  
Shuanglin Luo ◽  
Xingwei Zhang ◽  
Yonghua Cai ◽  
Fangqin Xue ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Mucinous Carcinoma ◽  
Molecular Signature ◽  
Response To Treatment ◽  
Mutation Rates ◽  
Genomic Features ◽  
Genomic Landscape ◽  
Comprehensive Genomic Profiling ◽  
New Treatment ◽  
Generation Sequencing

Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC. HER2 amplification and TP53 and APC mutation rates were lower, whereas SMAD4, PIK3CA, ACVR2A, KMT2D, LRP1, TGFBR2, GRIN2A, BRAF V600E, PTEN, and BRCA2 mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF-β pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.

scholarly journals Congenital Oral Squamous Cell Carcinoma in a Suckling Piglet

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Jasmine Hattab ◽  
Abigail Rose Trachtman ◽  
Pietro Giorgio Tiscar ◽  
Marco Di Domenico ◽  
Jessica Maria Abbate ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lower Lip ◽  
Papillomavirus Infection ◽  
First Case ◽  
Suckling Piglet ◽  
Generation Sequencing ◽  
Histopathological Investigation

A 3-week-old suckling piglet spontaneously died after septicemic colibacillosis. At postmortem examination, bulging and ulcerated lesions were seen, affecting the oral mucosa on the inner surface of the lower lip. After histopathological investigation, the diagnosis of congenital oral squamous cell carcinoma was made. To the best of our knowledge, this is the first case of congenital oral squamous cell carcinoma ever described. A relationship has been shown or suggested between papillomavirus infection and oral squamous cell carcinoma in humans and animals. However, next-generation sequencing study did not demonstrate any papillomavirus sequences in the case reported herein.

scholarly journals Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia

2020 ◽  
Author(s):  
Jessica E. Manning ◽  
Jennifer A. Bohl ◽  
Sreyngim Lay ◽  
Sophana Chea ◽  
Ly Sovann ◽  
...  
Keyword(s):  
Disease Outbreaks ◽  
Bioinformatics Pipeline ◽  
Illumina Platform ◽  
Resource Limited ◽  
First Case ◽  
Rapid Production ◽  
Public Health Information ◽  
Pathogen Genome ◽  
Generation Sequencing

AbstractRapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia’s first case of COVID-2019.

Comutation of PIK3CA and TP53 in Residual Disease After Preoperative Anti-HER2 Therapy in ERBB2 (HER2)-Amplified Early Breast Cancer

2019 ◽  
pp. 1-26
Author(s):  
Frankie Ann Holmes ◽  
Maren K. Levin ◽  
Ying Cao ◽  
Sohail Balasubramanian ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Residual Disease ◽  
Preoperative Treatment ◽  
Next Generation ◽  
Her2 Positive ◽  
Genomic Alterations ◽  
Pik3ca Mutations ◽  
Her2 Breast Cancer ◽  
Generation Sequencing

PURPOSE To identify proteomic and genomic alterations in residual disease (RD) for human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC) after preoperative trastuzumab (H), lapatinib (L), or both (H+L) in combination with chemotherapy. PATIENTS AND METHODS Patients with stage II/III HER2+ BC (n = 100) were randomly assigned to preoperative treatment with H versus L 1,250mg versus H+L (L: 750 to 1,000 mg) plus 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel. After receiving institutional review board–approved informed consent, targeted next-generation sequencing was performed on 20 patients’ formalin-fixed paraffin embedded tumors to characterize genomic alterations across 287 cancer-related genes. Reverse phase protein array (RPPA) analysis was performed on both the baseline biopsy and RD specimens, when available. RESULTS Two of 20 RD tissues were HER2 negative per next-generation sequencing; one sample had insufficient tissue. Of six pretreatment biopsy specimens, four were comutated with TP53 and PIK3CA. Of 17 HER2+ RD, seven specimens (41%) had PIK3CA mutations always comutated with TP53, and four (24%) also had concurrent CDK12 amplification. Overall, CDK12 amplification was observed in eight of the 17 (47%) HER2+ RD specimens. A total of 12 RD specimens (71%) had TP53 mutations. Although prevalence of individual TP53 and PIK3CA mutations was only modestly higher than published estimates for those in HER2+ primary BCs (55% and 32% for TP53 and PIK3CA, respectively), prevalence of these as comutations appeared higher (41%), compared with less than 10% in several series. On RPPA analysis of the RD tissue with comutations, the strongest Spearman ρ correlations were limited to EGFR and phospho-AKT (ρ, 0.999; P = .019) and phospho-mTOR and phospho-S6 ribosomal protein (ρ, 0.994; P = .048). CONCLUSION HER2-amplified RD tissue after preoperative H, L, or H+L plus chemotherapy was enriched for PIK3CA and TP53 comutations, and the RD tissue demonstrated activation of EGFR/AKT/mTOR signaling on RPPA.

scholarly journals A Canadian guideline on the use of next-generation sequencing in oncology

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
S. Yip ◽  
A. Christofides ◽  
S. Banerji ◽  
M. R. Downes ◽  
I. Izevbaye ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Best Practices ◽  
Sample Selection ◽  
Molecular Profile ◽  
Next Generation ◽  
Canadian Guideline ◽  
Molecular Tests ◽  
Management Guidance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Rapid advancements in next-generation sequencing (ngs) technology have created an unprecedented opportunity to decipher the molecular profile of tumours to more effectively prevent, diagnose, and treat cancer. Oncologists now have the option to order molecular tests that can guide treatment decisions. However, to date, most oncologists have received limited training in genomics, and they are now faced with the challenge of understanding how such tests and their interpretation align with patient management. Guidance on how to effectively use ngs technology is therefore needed to aid oncologists in applying the results of genomic tests. The Canadian guideline presented here describes best practices and unmet needs related to ngs-based testing for somatic variants in oncology, including clinical application, assay and sample selection, bioinformatics and interpretation of reports performed by laboratories, patient communication, and clinical trials.

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