Genetic analysis of colorectal cancers in young patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 632-632
Author(s):  
Andrea M. Abbott ◽  
Nishi Kothari ◽  
Jamie K. Teer ◽  
Thejal Srikumar ◽  
Richard D. Kim ◽  
...  
Keyword(s):  
Large Scale ◽  
Scale Validation ◽  
Young Patients ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Cancer Genes ◽  
Old Patients ◽  
Younger Patients ◽  
Exact Test ◽  
Worse Prognosis

632 Background: The incidence of colorectal cancer (CRC) is increasing in adults <50 years old and these cases may be associated with a worse prognosis. Despite our growing understanding of genetic conditions, a substantial number of CRC in young patients are classified as sporadic but may harbor unique molecular changes. We sought to compare profiles of genetic alterations between young and old patients who lack defects in known hereditary cancer genes. Methods: 283 CRC cases diagnosed between 1998 and 2010 were analyzed by targeted exome sequencing using the Illumina NGS platform with 50-100x coverage. Filtering of normal variants was performed using 1000 Genomes to enrich for somatic mutations which were then limited to those predicted to alter protein sequence. The younger and older cohorts were defined as ≤45 and ≥65 years old at diagnosis, respectively. Patients found to be MSI-high (n= 2 young, 50 old) or with a known hereditary syndrome (n=6) were excluded. For this preliminary screen, Fisher’s Exact test was used to detect differences in mutation frequencies. Results: A total of 195 older and 30 younger patients with median ages of 73 (range 65-93) and 42 (range 30-45) years respectively, were analyzed. We identified 57 genes with significant differential mutation frequencies. The top ten genes mutated with increased in frequency in the younger cohort are shown in Table 1. Conclusions: In this exploratory project, we identified mutations that occurred more frequently in younger CRC patients. Large scale validation of these findings and application of this approach may lead to novel screening and treatment strategies in younger patients [Table: see text]

Abstract 14178: Characteristics and Outcomes of Young ST Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Benjamin W Tung ◽  
Zhe Yan Ng ◽  
William Kristanto ◽  
Kalyar W Saw ◽  
winnie C sia ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Older Patients ◽  
Young Patients ◽  
Percutaneous Intervention ◽  
Old Patients ◽  
Younger Patients ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Primary Percutaneous Intervention

Introduction: ST-segment elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality leading to loss of productivity and productive life years, especially in younger patients. Understanding the characteristics of younger patients with STEMI and their outcomes could help focus public health efforts in STEMI prevention within a population. Aim: This study aims to compare the characteristics and outcomes of younger versus older patients with STEMI undergoing primary percutaneous intervention (PPCI). Methods: Data from the Coronary Care Unit database of the National University Hospital between July 2015 to June 2019 was reviewed. Patients were divided into Young (<50 years old) or Old (≥50 years old) groups. Results: Of the 1818 consecutive patients with STEMI and underwent PPCI, 465 (25.6%) were Young patients with mean age 43±4.9 years old as compared to Old patients with mean age 63.2±9.4 years old. Young patients were more likely to be male (94% vs. 85%, p<0.0001), current smokers (61.1% vs. 42.6%, p<0.0001), of Indian ethnicity (32% vs. 16.3%, p<0.0001), and had family history of myocardial infarction (MI) (18.1% vs. 9.5%, p<0.0001). Compared to Old patients, Young patients had better post-MI left ventricular ejection fraction (49.5±10.7 vs. 47.8±11.6, p=0.007) with fewer of them suffered from cardiogenic shock (7.1% vs. 13.2%, p<0.0001), and had lower mortality at one year (3.4% vs. 10.4%, p<0.0001). Although diabetes, hypertension and hyperlipidemia was less common among the Young patients when compared to the Old, the prevalence was high in the range of 28 to 38% (Table 1). Conclusions: A sizable proportion of STEMI patients are younger than 50 years old. The risk profile of these younger patients can be attributed to constitutional factors and smoking but other cardiovascular risk factors are also prevalent among them. Although mortality is lower among the younger than the older patients, it is not negligible.

PS01.162: IS THERE A DIFFERENCE IN SURVIVAL BETWEEN YOUNGER AND OLDER GASTRIC CANCER (INCLUDING AEG II AND AEG III) PATIENTS AFTER GASTRECTOMY?

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 95-95
Author(s):  
Benjamin Babic ◽  
Florian Matthias Corvinus ◽  
Edin Hadjijusufovic ◽  
Evangelos Tagkalos ◽  
Hauke Lang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Subtotal Gastrectomy ◽  
Young Patients ◽  
Western World ◽  
Old Patients ◽  
Younger Patients ◽  
Significant Difference

Abstract Background The incidence of gastric cancer decreases in the western world, however, it remains one of the most common diseases (1). There is just little data from Europe comparing the outcome of young and elderly gastric cancer patients. This study compares, depending on the age of 266 patients, the outcome of 266 consecutive gastrectomy cases due to gastric cancer Methods 266 consecutive patients with gastric cancer received a gastrectomy between 2008–2016 at our comprehensive cancer centre. The mean age of the patients in this study was 64 years old (21- 93 years). All patients were followed up regarding survival. The patients were separated in 6 different groups, depending on the age at the time of operation. The different groups were re-analysed and compared to each other regarding median and 5-year survival. Results In this collective the 5-year survival rate for all patients was 43%. There were more diffuse type adenocarcinomas in Patients < 40 years. In younger patients the tumour was staged in an advanced stadium compared to the elderly patients group. There is a significantly higher 5-year survival rate for younger patients after gastrectomy. There is no significant difference, when separating patient groups in to decades of age. Conclusion Young patients have a higher 5-year survival rate after gastrectomy compared to old patients. However, comparing patients from chronologic age in decades, the significance is not reproducible. Therefore gastrectomy or subtotal gastrectomy is the determining therapeutic approach for gastric cancer with an acceptable outcome in both young and elderly patients. Older patients might have an lower 5 year survival rate not only due to the cancer or the surgical therapy itself, it is related to comorbidities and a lower rate in neoadjuvant therapy as well Disclosure All authors have declared no conflicts of interest.

scholarly journals ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome

2016 ◽  
Vol 175 (5) ◽  
pp. R203-R217 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Pilar Santisteban
Keyword(s):  
Thyroid Cancer ◽  
Cancer Genomics ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Cancer Genome ◽  
Molecular Pathogenesis ◽  
Cancer Genes ◽  
New Information ◽  
Novel Treatment Strategies ◽  
And Behavior

Thyroid cancer is the most common endocrine malignancy giving rise to one of the most indolent solid cancers, but also one of the most lethal. In recent years, systematic studies of the cancer genome, most importantly those derived from The Cancer Genome Altas (TCGA), have catalogued aberrations in the DNA, chromatin, and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Cancer genomics is therefore providing new information on cancer development and behavior, as well as new insights into genetic alterations and molecular pathways. From this genomic perspective, we will review the main advances concerning some essential aspects of the molecular pathogenesis of thyroid cancer such as mutational mechanisms, new cancer genes implicated in tumor initiation and progression, the role of non-coding RNA, and the advent of new susceptibility genes in thyroid cancer predisposition. This look across these genomic and cellular alterations results in the reshaping of the multistep development of thyroid tumors and offers new tools and opportunities for further research and clinical development of novel treatment strategies.

Genomic profiling of variant urinary tract tumor histologies.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 450-450
Author(s):  
Amin Nassar ◽  
Kent William Mouw ◽  
Catherine Curran ◽  
Archana Agarwal ◽  
Andres Acosta ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Invasive Disease ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Cancer Genes ◽  
Exact Test ◽  
Genetic Features ◽  
Variant Histology ◽  
Mixed Histology ◽  
Muscle Invasive

450 Background: Little is known about the genomic features of rare histologic variants of urinary tract (UT) tumors. The purpose of this study is to compare the pattern of genetic alterations in UT tumors with adenocarcinoma (AD), small cell (SC), or squamous cell (SQ) histology to UT tumors with urothelial carcinoma (UC) histology. Methods: We identified patients with pure variant (AD, SC, or SQ) or UC histology evaluated at Dana Farber Cancer Institute (DFCI). Tumors with mixed histology were excluded. We employed Oncopanel, which assesses 275-447 cancer genes for somatic mutations and copy number variations (CNVs). Alterations observed at an allele frequency > 0.1% in the ExAC database were assumed to be germline variants and were excluded. Mutation frequencies, CNVs, and tumor mutation burden (TMB) were determined for AD, SC, SQ, and UC, and were compared using the Fisher’s Exact test and Kruskall Wallis Test. Nominal p values were obtained, and fdr correction was employed (q < 0.1). Results: Genetic data was available for 11 AD, 6 SC, 9 SQ, and 120 UC tumors. All patients had muscle-invasive disease. The mean age was 67.8 years and 74% of patients were male. Overall, UC had significantly higher TMB than AD (median = 9.5 vs median = 6 respectively, p = 0.03). There were no significant differences in the CNV count among the four subtypes. Statistically significant differences in genetic alterations by subtype are shown in the Table. ARID1A and KDM6A mutations were less common in the variant histologies; while DICER1, FBXW7, MAP2K4, and MYB alterations were higher in ≥1 variant histology. RB1 and TP53 mutations were enriched in SC tumors while SMAD4 alterations were enriched in AD tumors. Conclusions: Genetic features of variant histology UT tumors differ from those seen in UC, suggesting biological differences and possibly different therapies. Validation in larger datasets is warranted. [Table: see text]

scholarly journals Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies

2020 ◽  
Vol 21 (11) ◽  
pp. 4012 ◽  
Author(s):  
Julita Machlowska ◽  
Jacek Baj ◽  
Monika Sitarz ◽  
Ryszard Maciejewski ◽  
Robert Sitarz
Keyword(s):  
Gastric Cancer ◽  
Genetic Factors ◽  
Young Patients ◽  
Treatment Strategies ◽  
Disease Process ◽  
Genetic Alterations ◽  
Cancer Epidemiology ◽  
Epigenetic Alterations ◽  
Environmental Carcinogens ◽  
Progressive Development

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.

Prognostic Impact of Mutations in the Nucleophosmin (NPM1) and of the FMS-Related Tyrosine Kinase 3 (FLT3) Genes in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Intensive Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2542-2542 ◽  
Author(s):  
Anne Etienne ◽  
Cecile Borel ◽  
Sarah Reutenauer ◽  
Sylviane Olschwang ◽  
Marie-Joelle Mozziconacci ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Young Patients ◽  
Genetic Alterations ◽  
Prognostic Impact ◽  
Wild Type ◽  
Old Patients ◽  
Npm1 Mutation ◽  
Female Patients ◽  
Cell Counts ◽  
Significant Difference

Abstract AML is a heterogeneous disease and the actual most reliable prognostic factor is the karyotype. Mutations of NPM1 and FLT3 constitute the most frequent molecular genetic alterations in patients with AML. Their prognostic impact is now well recognized, especially in young patients with intermediate prognosis karyotype. However few studies have focused on elderly patients. We retrospectively studied the prevalence of NPM1 mutation and FLT3 internal tandem duplications (ITD) and its association with complete remission (CR) and survival in 86 patients aged 61 years or older treated between 1996 and 2007 for acute non promyelocytic leukemia with intermediate karyotype in the Institut Paoli-Calmettes, Marseille, and the university hospital of Toulouse. All patients received intensive induction chemotherapy (“3+7” regimen). Median age was 70 years (range, 61–79). The median follow-up of surviving patients was 34 months. 44 patients (51%) had NPM1 mutation and 21 had FLT3-ITD (24%). In the NPM1 mutated group, there were significantly more: female patients, absence of antecedent hematologic disorder, de novo AML, and low CD34 expression. In the FLT3-ITD group, there were significantly more: female patients, increased white blood cell counts and peripheral blood blasts. Overall CR rate was 67%; median disease free survival (DFS) and overall survival (OS) were 11 and 10 months, respectively. CR rate was negatively associated with a poor performans status and a high score previously described including assessment of comorbidities (Etienne et al., Cancer2007; 109(7):1376–83). CR rate was 57% versus 72% for patients with FLT3-ITD compared to patients with wild-type FLT3 (p 0.2), and 64% versus 71% for the NPM1 mutated group compared with the NPM1 non-mutated group (p 0.5). Median OS was 6 months versus 12 months for patients with FLT3-ITD mutation versus wild type patients (p = 0.04). Median OS was 9 months for patients with NPM1 mutation and did not differ from non-mutated patients. No significant difference in term of CR rate and OS was found between the 29 patients carrying NPM1 mutation without FLT3-ITD and the 57 other patients without NPM1 mutation or with FLT3-ITD. Median DFS was 21 months versus 9 months for these two groups, respectively (p 0.2). These results confirm the prognostic impact of FLT3-ITD in our series of old patients with AML. Unlike young patients, NPM1 mutated elderly patients have a similar outcome than NPM1 wild type patients. The absence of prognostic impact of NPM1 mutation without FLT3-ITD has to be validated on larger prospective cohort. FLT3 status should be taken into account for treatment choices in elderly patients.

scholarly journals AB0943 INFECTIOUS SPONDYLODISCITIS OF THE ELDERLY: CHARACTERISTICS AND OUTCOMES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1770.3-1770
Author(s):  
J. Mahbouba ◽  
O. Jomaa ◽  
S. Zrour ◽  
I. Bejia ◽  
M. Touzi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Spinal Cord ◽  
Young Patients ◽  
The Elderly ◽  
Neurological Complications ◽  
University Hospital ◽  
Biological Assessment ◽  
Old Patients ◽  
Younger Patients ◽  
Infectious Spondylodiscitis

Background:Spondylodiscitis still frequent. It affects both old and young patients. It makes diagnostic and therapeutic difficulties.Objectives:to identify the characteristics and outcomes of infectious spondylodiscitis (ISD) in patients over 65 years old.Methods:A monocentric retrospective study including patients hospitalized for ISD in the rheumatology department of university hospital of Monastir,TUNISIA between January 2009 and August 2019.Results:Among 70 patients with ISD, 21 (11 male, 10 female) or 30% are over 65 years old. The average age was 70.6 years (65-82 years). History of diabetes (n = 9), hypertension (n = 9), hemodialysis (n = 5), heart disease (n = 5) were the most risk factors reported, while in younger patients, spinal surgery, epidural infiltrations and long-term general corticosteroid therapy were the main risk factors. The mean time for consultation was 142.3± 73 days longer than for younger patients. Fever was present in 0,14% of cases. Assessment time found that already 5 patients had paraplegia or spinal cord compression. 19/21 patients had epiduritis on spinal cord MRI. Soft tissue abscesses were present in close rate in both younger and old patients. Biological assessment showed an inflammatory syndrome and hyperleukocytosis in 92% and 38% of patients respectively (compared to 73% and 27% in younger patients). Germs ware identified in 14 patients (47.3%). Common germs were the most involved (12 patients), while in younger patients, specific- germs were the most reported. Follow up has shown that neurological sequelae are more prevalent in elderly.Conclusion:ISD in patients over 65 years old require a careful attension in therapeutic management given that age according to this study seems to influence the prognosis. In fact, these patients are more susceptible to disability due to neurological complications.References:doi: 10.1016/j.medcli.2017.07.027.doi: 10.1016/j.jinf.2008.02.005.Acknowledgments:Rheumatology departmentDisclosure of Interests:None declared

Genomic landscape and clinicopathological characteristics of lung cancer in young Chinese patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13520-e13520
Author(s):  
Jiexia Zhang ◽  
Xiaoling Tong ◽  
Hua Bao ◽  
Xue Wu ◽  
Xiaonan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Large Scale ◽  
Young Patients ◽  
Clinical Information ◽  
Copy Number Gain ◽  
Genetic Alterations ◽  
Young Female ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Life Styles

e13520 Background: Approximately 2-3% of lung cancer (LC) was found in very young patients (≤ 45 years old) and they were reported to have different clinical characteristics and genetic profiles when compared to older patients. However, it is still lack of large-scale genomic studies that could provide deep insights into the tumorigenesis, precision treatment and prognosis for this particular population. Methods: Clinically annotated data of targeted next generation sequencing (NGS) on 7858 tumor tissue specimens from LC patients were analyzed. For all specimens, a total of 422 or 425 cancer-related genes were interrogated with a mean coverage depth greater than 500x. Results: Of 7858 LC cases, 814 of them were younger than 45 (age at diagnosis), which were compared to 7044 old LC cases ( > 45 years old). Clinical information showed that young LC are more prevalent in female, to be more advanced disease and to have more adenocarcinoma in histology. Somatic genomic data analysis revealed that compared to old LC, young LC has significantly higher ALK/ROS1/RET fusions, ERBB2 mutations and 5q amplification(FDR < 0.1), but lower mutational frequencies in KRAS, CDKN2A, ERBB4, FAT1, NF1, lower copy number gain (CNG) of PIK3CA, MDM2, FGFR1, and less 5q deletion(FDR < 0.1). Interestingly, in young LC, genetic differences between female and male are not significant, with TP53 and EGFR being most frequently mutated in both sexes. Similarly, the differences between young and old female LC are also limit, with young female LC having more ALK fusions (13.43% vs. 5.1%, FDR < 0.01), less EGFR mutations and MDM2 CNG than old female. On the contrary, male patients demonstrated much wide disparity between young and old LC: young LC was enriched with ALK/ROS1/RET/ERBB2 fusions and mutations in EGFR, ERBB2 and SMAD2, while old LC have more mutations in KRAS, TP53, CDKN2A, and CNG of PIK3CA (all FDR < 0.1). We also found that EGFR exon19 deletion (19del) was significantly enriched in young LC, especially in male, while p.L858R showed preference in old LC. Conclusions: The data suggest that the prevalence of different genetic alterations is both age and sex related. The high level of ALK/ROS1/RET fusions and less CNV in young LC could potentially lead to more effective treatment and better prognosis. We also noted that genomic alterations in young LC were not significantly different across sexes, but the disparity by sex was enormously enlarged in old LC, which might be correlated to their life-long exposures, such as smoking, life styles and sex-affected factors.

scholarly journals Identification of Relevant Genetic Alterations in Cancer using Topological Data Analysis

2020 ◽  
Author(s):  
Raúl Rabadán ◽  
Yamina Mohamedi ◽  
Udi Rubin ◽  
Tim Chu ◽  
Oliver Elliott ◽  
...  
Keyword(s):  
Data Analysis ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Fold Increase ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Topological Data Analysis ◽  
Integrated Analysis ◽  
Cancer Genes ◽  
Topological Data

AbstractLarge-scale cancer genomic studies enable the systematic identification of mutations that lead to the genesis and progression of tumors, uncovering the underlying molecular mechanisms and potential therapies. While some such mutations are recurrently found in many tumors, many others exist solely within a few samples, precluding detection by conventional recurrence-based statistical approaches. Integrated analysis of somatic mutations and RNA expression data across 12 tumor types reveals that mutations of cancer genes are usually accompanied by substantial changes in expression. We use topological data analysis to leverage this observation and uncover 38 elusive candidate cancer-associated genes, including inactivating mutations of the metalloproteinase ADAMTS12 in lung adenocarcinoma. We show that ADAMTS12−/− mice have a five-fold increase in the susceptibility to develop lung tumors, confirming the role of ADAMTS12 as a tumor suppressor gene. Our results demonstrate that data integration through topological techniques can increase our ability to identify previously unreported cancer-related alterations.

scholarly journals Age and Gender Influence Reaction to Glaucoma Diagnosis

2018 ◽  
Vol 12 (2) ◽  
pp. 85 ◽  
Author(s):  
Gemma Caterina Maria Rossi ◽  
Keyword(s):  
Open Angle Glaucoma ◽  
Young Patients ◽  
Fisher Exact Test ◽  
Physician Patient Relationship ◽  
Chi Square ◽  
Younger Patients ◽  
Exact Test ◽  
Glaucoma Diagnosis ◽  
More Care ◽  
And Gender

Purpose:To consider the effects of announcing the diagnosis of glaucoma and to record the patients’ knowledge of the disease.Methods:Patients treated for primary open angle glaucoma completed a questionnaire at a regular visit to their ophthalmologist. The questions recorded the patients’ reaction to the diagnosis and the information received. Patients have been studied by sex and age. Results are presented as frequencies and percentages. Differences were evaluated by means of Chi-square statistic or Fisher exact test.Results:One hundred and twelve patients completed the questionnaire. Eighty-seven (77.7%) patients reported negative emotions after diagnosis: 41 (36.6%) were afraid of going blind and 31 (27.7%) experienced anxiety (younger patients more than older patients; p=0.048). Nearly half of the patients declared that they had modified their behaviour, indicating they took more care of their eyes (mainly young patients and women). Seventy-seven (68.7%) patients were satisfied with the information and care given. Only 26 (23.2%) cited inheritance and elevated intraocular pressure as causes of glaucoma. Many patients asked for more information on the causes, evolution and prevention of the disease. Younger patients (n=40; 93.0%) and women (n=52; 89.6%) asked more questions.Conclusion:Announcing a diagnosis of glaucoma is a fundamental step in the physician–patient relationship. This disease negatively influences quality of life due to its chronic nature: better patient-tailored information is necessary. Although age and sex influence the reactions to diagnosis and the satisfaction with the information and care given, most of the patients were satisfied with their eye specialists.

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