scholarly journals Mutational Profile of Driver Genes in Brazilian Melanomas

2019 ◽  
pp. 1-14 ◽  
Author(s):  
Anna Luiza S.A. Vicente ◽  
Camila S. Crovador ◽  
Graziela Macedo ◽  
Cristovam Scapulatempo-Neto ◽  
Rui M. Reis ◽  
...  
Keyword(s):  
Skin Color ◽  
Hot Spot ◽  
Survival Rates ◽  
Tumor Location ◽  
Superficial Spreading ◽  
Driver Genes ◽  
Tert Promoter ◽  
Mutational Status ◽  
Black Skin ◽  
Anatomic Locations

PURPOSE Mutation testing of the key genes involved in melanoma oncogenesis is now mandatory for the application of targeted therapeutics. However, knowledge of the mutational profile of melanoma remains largely unknown in Brazil. PATIENTS AND METHODS In this study, we assessed the mutation status of melanoma driver genes BRAF, NRAS, TERT, KIT, and PDGFRA in a cohort of 459 patients attended at Barretos Cancer Hospital between 2001 and 2012. We used polymerase chain reaction followed by Sanger sequencing to analyze the hot spot mutations of BRAF exon 15 (V600E), NRAS (codons 12/13 and 61), TERT (promoter region), KIT (exons 9, 11, 13, and 17), and PDGFRA (exons 12, 14, and 18) in tumors. The mutational profile was investigated for associations with demographic, histopathologic, and clinical features of the disease. RESULTS The nodular subtype was most frequent (38.9%) followed by the superficial spreading subtype (34.4%). The most frequent tumor location was in the limbs (50.0%). The mutation rates were 34.3% for TERT and 34.1% for BRAF followed by NRAS (7.9%), KIT (6.2%), and PDGFRA (2.9%). The BRAF ( P = .014) and TERT ( P = .006) mutations were associated with younger patients and with different anatomic locations, particularly in the trunk, for the superficial spreading and nodular subtypes, respectively ( P = .0001 for both). PDGFRA mutations were associated with black skin color ( P = .023) and TERT promoter mutations with an absence of ulceration ( P = .037) and lower levels of lactate dehydrogenase. There was no association between patient survival rates and mutational status. CONCLUSION The similar mutational profile we observe in melanomas in Brazil compared with other populations will help to guide precision medicine in this country.

Retrospective analysis of clinical characteristics of mCRC patients receiving three or more lines of chemotherapy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 682-682
Author(s):  
Pilar Garcia Alfonso ◽  
Íñigo Martínez Delfrade ◽  
Javier Soto Alsar ◽  
Marianela Bringas Beranek ◽  
Natalia Gutiérrez Alonso ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Clinical Characteristics ◽  
Survival Rates ◽  
Tumor Resection ◽  
Complete Response ◽  
Tumor Location ◽  
First Line ◽  
Mutational Status

682 Background: Prognostic and predictive factors are becoming more important in mCRC patients, and may have an impact in overall survival and in the number of lines of chemotherapy that a patient can receive. Methods: We conducted a retrospective analysis of 334 patients with mCRC. We analyzed the clinical characteristics of 113 (33.8%) mCRC patients who received ≥3 lines of chemotherapy. We apply the statistical test Chi square in order to identify significant association. Results: Several characteristics were significantly associated with receiving ≥ 3 lines of chemotherapy (n = 113): age < 80 years (n = 93, OR = 3.07, p = 0.001), ECOG 0-1 (n = 98, OR = 3.21, p = 0.055), primary tumor resection (n = 62, OR = 2.36, p = 0.000) and resection of metastases (n = 56, OR = 2.07, p = 0.002). Partial or complete response rate in the first line of chemotherapy was also significantly associated with receiving ≥ 3 lines of treatment (n = 65, p = 0.011). Tumor mutational status was analyzed in 333 patients: KRAS mutation was detected in 163 over 333 patients genotyped (48.9%), NRAS in 25/206 (12.1%), BRAF in 15/217 (6.9%) and PI3K in 31/213 (14.5%). In the group of patients receiving ≥ 3 lines of chemotherapy (n = 113): KRAS mutation was found in 60/113 patients (53.1%), NRAS in 5/77 (6.5 %), BRAF in 5/84 (5.9%) and PI3K in 8/80 (11.1%). Tumor mutations were not significantly associated with ≥ 3 lines of chemotherapy. No significant association was found between sex, tumor location (right [n = 33, 29.2%] or left [n = 76, 73%]), liver or lung isolated metastases and 3 or later lines of chemotherapy. We also performed in our database a survival analysis in the 334 patients: those who received ≥3 lines of chemotherapy had significantly higher survival rates (median OS 18 m in the group of < 3 lines of treatment vs. 37.2 m in the group of ≥ 3 lines of chemotherapy, HR = 1,6; CI 95% 1,2-2.1; p < 0,001). Conclusions: This retrospective analysis showed that mCRC patients with < 80 years, ECOG 0-1, primary tumor and or metastases resected and those with complete or partial response in the first line of treatment have a higher probability of receiving ≥ 3 lines of chemotherapy. [Table: see text]

scholarly journals TERT Promoter Mutation Analysis of Whole-Organ Mapping Bladder Cancers

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 230
Author(s):  
Veronika Weyerer ◽  
Markus Eckstein ◽  
Pamela L. Strissel ◽  
Adrian Wullweber ◽  
Fabienne Lange ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Telomere Length ◽  
Hot Spot ◽  
Tumor Development ◽  
Non Invasive ◽  
Tert Promoter ◽  
Mutational Status ◽  
Tert Promoter Mutations ◽  
Promoter Mutations ◽  
Normal Urothelium

Background: Multifocal occurrence is a main characteristic of urothelial bladder cancer (UBC). Whether urothelial transformation is caused by monoclonal events within the urothelium, or by polyclonal unrelated events resulting in several tumor clones is still under debate. TERT promoter mutations are the most common somatic alteration identified in UBC. In this study, we analyzed different histological tissues from whole-organ mapping bladder cancer specimens to reveal TERT mutational status, as well as to discern how tumors develop. Methods: Up to 23 tissues from nine whole-organ mapping bladder tumor specimens, were tested for TERT promoter mutations including tumor associated normal urothelium, non-invasive urothelial lesions (hyperplasia, dysplasia, metaplasia), carcinoma in situ (CIS) and different areas of muscle invasive bladder cancers (MIBC). The mutational DNA hotspot region within the TERT promoter was analyzed by SNaPshot analysis including three hot spot regions (−57, −124 or −146). Telomere length was measured by the Relative Human Telomere Length Quantification qPCR Assay Kit. Results: TERT promoter mutations were identified in tumor associated normal urothelium as well as non-invasive urothelial lesions, CIS and MIBC. Analysis of separate regions of the MIBC showed 100% concordance of TERT promoter mutations within a respective whole-organ bladder specimen. Polyclonal events were observed in five out of nine whole-organ mapping bladder cancers housing tumor associated normal urothelium, non-invasive urothelial lesions and CIS where different TERT promoter mutations were found compared to MIBC. The remaining four whole-organ mapping bladders were monoclonal for TERT mutations. No significant differences of telomere length were observed. Conclusions: Examining multiple whole-organ mapping bladders we conclude that TERT promoter mutations may be an early step in bladder cancer carcinogenesis as supported by TERT mutations detected in tumor associated normal urothelium as well as non-invasive urothelial lesions. Since mutated TERT promoter regions within non-invasive urothelial lesions are not sufficient alone for the establishment of cancerous growth, this points to the contribution of other gene mutations as a requirement for tumor development.

scholarly journals Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chaiwat Tawarungruang ◽  
Narong Khuntikeo ◽  
Nittaya Chamadol ◽  
Vallop Laopaiboon ◽  
Jaruwan Thuanman ◽  
...  
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Cox Regression ◽  
Survival Rates ◽  
Care Program ◽  
Tumor Location ◽  
Northeast Thailand ◽  
Curative Surgery

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

Transcriptome reveals genes involving in black skin color formation of ducks

2021 ◽  
Vol 43 (2) ◽  
pp. 173-182
Author(s):  
Lei Wang ◽  
Hehe Liu ◽  
Bo Hu ◽  
Jiwei Hu ◽  
Hengyong Xu ◽  
...  
Keyword(s):  
Skin Color ◽  
Color Formation ◽  
Black Skin

Mini-review: Childhood-onset Craniopharyngioma

2021 ◽  
Author(s):  
Anna Otte ◽  
Hermann L Müller
Keyword(s):  
Quality Of Life ◽  
Survival Rates ◽  
Residual Tumor ◽  
Tumor Location ◽  
Multidisciplinary Teams ◽  
Low Grade ◽  
Childhood Onset ◽  
Severe Impairment ◽  
Grade Malignancy

Abstract Craniopharyngiomas are rare embryonic malformational tumors of the sellar/parasellar region, classified by the WHO as tumors with low-grade malignancy (WHO I°). The childhood adamantinomatous subtype of craniopharyngioma is usually cystic with calcified areas. At the time of diagnosis, hypothalamic/pituitary deficits, visual disturbances and increased intracranial pressure are major symptoms. The treatment of choice in case of favorable tumor location (without hypothalamic involvement) is complete resection. It is important to ensure that optical and hypothalamic functionality are preserved. In case of unfavorable tumor location, i.e. with hypothalamic involvement, a hypothalamus-sparing surgical strategy with subsequent local irradiation of residual tumor is recommended. In the further course of the disease, recurrences and progression often occur. Nevertheless, overall survival rates are high at 92%. Severe impairment of quality of life and comorbidities such as metabolic syndrome, hypothalamic obesity and neurological consequences can be observed in patients with disease- and/or treatment-related lesions of hypothalamic structures. Childhood-onset craniopharyngioma frequently manifests as a chronic disease so that patients require lifelong, continuous care by experienced multidisciplinary teams to manage clinical and quality of life consequences.For this review, a search for original articles and reviews published between 1986 and 2020 was performed in Pubmed, Science Citation Index Expanded, EMBASE and Scopus. The search terms used were “craniopharyngioma, hypothalamus, pituitary obesity, irradiation, neurosurgery”.

PATH-40. SPORADIC NF2 WILD-TYPE MULTIPLE MENINGIOMAS HARBOR DISTINCT DRIVER MUTATIONS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi124-vi124
Author(s):  
Insa Prilop ◽  
Thomas Pinzer ◽  
Daniel Cahill ◽  
Priscilla Brastianos ◽  
Gabriele Schackert ◽  
...  
Keyword(s):  
Hot Spot ◽  
Low Frequency ◽  
Neurofibromatosis Type ◽  
Driver Mutations ◽  
Wild Type ◽  
Driver Genes ◽  
Who Grade ◽  
Genetic Changes ◽  
Histologic Subtype ◽  
Multiple Meningiomas

Abstract OBJECTIVE Multiple meningiomas (MM) are rare and present a unique management challenge. While the mutational landscape of single meningiomas has been extensively studied, understanding the molecular pathogenesis of sporadic MM remains incomplete. The objective of this study is to elucidate the genetic features of sporadic MM. METHODS We identified nine patients with MM (n=19) defined as ≥2 spatially separated synchronous or metachronous meningiomas. We profiled genetic changes in these tumors using next-generation sequencing (NGS) assay that covers a large number of targetable and frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. RESULTS Most of MM were WHO grade 1 (n= 16, 84.2%). Within individual patients, no driver mutation was shared between separate tumors. All but two cases harbored different hot spot mutations in known meningioma-driver genes like TRAF7 (n= 5), PIK3CA (n= 4), AKT1 (n= 3), POLR2A (n=1) and SMO (n= 1). Moreover, individual tumors differed in histologic subtype in 8/9 patients. The low frequency of NF2 mutations in our series stands in contrast to previous studies that included hereditary cases arising in the setting of neurofibromatosis type 2 (NF2). CONCLUSIONS Our findings provide evidence for genomic inter-tumor heterogeneity and an independent molecular origin of sporadic NF2 wild-type MM. Furthermore, these findings suggest that genetic characterization of each lesion is warranted in sporadic MM.

scholarly journals Food Insecurity and Associated Factors in Brazilian Undergraduates during the COVID-19 Pandemic

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 358
Author(s):  
Bruna Leal Lima Maciel ◽  
Clélia de Oliveira Lyra ◽  
Jéssica Raissa Carlos Gomes ◽  
Priscilla Moura Rolim ◽  
Bartira Mendes Gorgulho ◽  
...  
Keyword(s):  
Food Insecurity ◽  
Diet Quality ◽  
Skin Color ◽  
Associated Factors ◽  
Mental Distress ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Black Skin ◽  
Logistic Regressions ◽  
Socio Economic Variables

Undergraduates may face challenges to assure food security, related to economic and mental distress, especially during the COVID-19 pandemic. This study aimed to assess food insecurity and its associated factors in undergraduates during the COVID-19 pandemic. An online cross-sectional study was conducted from August 2020 to February 2021 with 4775 undergraduates from all Brazilian regions. The questionnaire contained socio-economic variables, the validated Brazilian food insecurity scale, and the ESQUADA scale to assess diet quality. The median age of the students was 22.0 years, and 48.0% reported income decreasing with the pandemic. Food insecurity was present in 38.6% of the students, 4.5% with severe food insecurity and 7.7% moderate. Logistic regressions showed students with brown and black skin color/race presented the highest OR for food insecurity; both income and weight increase or reduction during the pandemic was also associated with a higher OR for food insecurity, and better diet quality was associated with decreased OR for food insecurity. Our study showed a considerable presence of food insecurity in undergraduates. Policy for this population must be directed to the most vulnerable: those with brown and black skin color/race, who changed income during the pandemic, and those presented with difficulties maintaining weight and with poor diet quality.

scholarly journals Advances in the management of craniopharyngioma in children and adults

2019 ◽  
Vol 53 (4) ◽  
pp. 388-396 ◽  
Author(s):  
Mojca Jensterle ◽  
Soncka Jazbinsek ◽  
Roman Bosnjak ◽  
Mara Popovic ◽  
Lorna Zadravec Zaletel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Tumor Location ◽  
Subtotal Resection ◽  
Metabolic Complications ◽  
Optimal Outcomes ◽  
Parasellar Region ◽  
Long Term Follow Up ◽  
Considerable Controversy

Abstract Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient’s quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor’s molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.

scholarly journals Intraductal Papillary Neoplasms of the Bile Duct

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Masayuki Ohtsuka ◽  
Hiroaki Shimizu ◽  
Atsushi Kato ◽  
Hideyuki Yoshitomi ◽  
Katsunori Furukawa ◽  
...  
Keyword(s):  
Bile Duct ◽  
Molecular Genetic ◽  
Intraepithelial Neoplasia ◽  
Mucinous Carcinoma ◽  
Tumor Location ◽  
Tubular Adenocarcinoma ◽  
Superficial Spreading ◽  
Genetic Changes ◽  
Intraductal Papillary Neoplasm ◽  
Radiologic Findings

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. IPNBs display a spectrum of premalignant lesion towards invasive cholangiocarcinoma. The most common radiologic findings for IPNB are bile duct dilatation and intraductal masses. The major treatment of IPNB is surgical resection. Ultrasonography, computed tomography, magnetic resonance image, and cholangiography are usually performed to assess tumor location and extension. Cholangioscopy can confirm the histology and assess the extent of the tumor including superficial spreading along the biliary epithelium. However, pathologic diagnosis by preoperative biopsy cannot always reflect the maximum degree of atypia, because IPNBs are often composed of varying degrees of cytoarchitectural atypia. IPNBs are microscopically classified into four epithelial subtypes, such as pancreatobiliary, intestinal, gastric, and oncocytic types. Most cases of IPNB are IPN with high-grade intraepithelial neoplasia or with an associated invasive carcinoma. The histologic types of invasive lesions are either tubular adenocarcinoma or mucinous carcinoma. Although several authors have investigated molecular genetic changes during the development and progression of IPNB, these are still poorly characterized and controversial.

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