scholarly journals Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kay Reen Ting ◽  
Pei Yi Ong ◽  
Samuel Ow Guan Wei ◽  
Rajeev Parameswaran ◽  
Chin Meng Khoo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cancer Genetics ◽  
Chinese Patients ◽  
Hereditary Cancer Syndrome ◽  
Limited Data ◽  
Cancer Syndrome ◽  
Causative Gene ◽  
Asian Patients ◽  
Pathogenic Variants ◽  
History Of

Abstract Background Hereditary paraganglioma (PGL) and pheochromocytoma (PCC) syndromes are rare conditions, with limited data on spectrum of causative gene variants of these syndromes in Asian patients. Methods We describe the clinical characteristics and genetic testing outcomes of patients with suspected hereditary PGL/PCC who were referred to a tertiary cancer genetics clinic in Singapore. Results Among 2196 patients with suspected hereditary cancer syndrome evaluated at the cancer genetics clinic from 2000 to 2019, 13/2196 (0.6%) patients fulfilled clinical suspicion for hereditary PGL/PCC syndrome. After genetic counselling, 10 patients underwent multi-gene next generation sequencing and deletion/duplication analysis, including SDHAF2, SDHA, SDHB, SDHC, SDHD, VHL, NF1, RET, MAX, and TMEM127. Seven of 10 patients (70%) were identified to carry pathogenic variants, including 3 unrelated Chinese patients with head and neck PGL who carried the same SDHD: c.3G > C (p.Met1Ile) variant that was previously reported to be a possible founder variant in Chinese, and 3 patients with urogenital PGL and 1 patient with retroperitoneal PGL who carried different SDHB variants. Variant carriers were younger, more likely to present with multiple tumours, or have family history of paraganglioma or pheochromocytoma, than non- variant carriers. Conclusion Hereditary PGL/PCC accounts for only 0.6% of patients seen in an adult cancer genetics clinic in Asia. SDHD and SDHB genes remain the most important causative genes of hereditary PGL/PCC in Asia even when patients are tested with multi-gene NGS panel.

scholarly journals The Hereditary Spectrum of Pancreatic Cancer: The Edmonton Experience

2004 ◽  
Vol 18 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Margaret Lilley ◽  
Dawna Gilchrist
Keyword(s):  
Pancreatic Cancer ◽  
At Risk ◽  
Family History ◽  
Hereditary Cancer ◽  
Cancer Genetics ◽  
Hereditary Cancer Syndrome ◽  
Molecular Testing ◽  
Cancer Syndrome ◽  
History Of ◽  
Cancer Syndromes

OBJECTIVE:Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes.METHODS:The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed.RESULTS:Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition.CONCLUSIONS:With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.

scholarly journals Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

2022 ◽  
Vol 11 ◽  
Author(s):  
Van Thuan Tran ◽  
Sao Trung Nguyen ◽  
Xuan Dung Pham ◽  
Thanh Hai Phan ◽  
Van Chu Nguyen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Hereditary Cancer ◽  
Carrier Frequency ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
Pathogenic Variants ◽  
History Of ◽  
Cancer Syndromes ◽  
History Of Cancer

BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.

scholarly journals Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Margaret Ward, DNP, APRN, AGNP-BC ◽  
Betty Elder, PhD, RN ◽  
Maryon Habtemariam, DNP, APRN
Keyword(s):  
Genetic Testing ◽  
Retrospective Analysis ◽  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Preventative Measures ◽  
Cancer Syndromes

It is estimated that 5% to 10% of all cancers are related to a hereditary cancer syndrome. However, specific cancers, such as pancreatic and ovarian cancers, are related to hereditary cancer syndromes 15% to 20% of the time. Genetic testing guidelines for hereditary cancer syndromes are frequently reviewed and updated by the National Comprehensive Cancer Network (NCCN). The purpose of this retrospective analysis is to identify carriers of pathogenic variants or hereditary cancer syndrome who do not meet NCCN criteria for testing and compare the results with previous studies. The data obtained can be used to provide recommendations to assess current guidelines for testing and evaluate the benefit of comprehensive panel testing vs. standard testing for specific hereditary cancer syndromes. This project is a retrospective review of clinical histories of patients who had multigene panel testing between September 2015 and February 2019 through a cancer outreach and risk assessment (CORA) program. Frequencies analyses were performed to analyze results. A total of 233 individuals were included in the analysis: 171 met BRCA1/2 testing criteria, 66 met Lynch syndrome criteria, and 4 met polyposis criteria. Of the individuals meeting established criteria for testing, 39 were identified with pathogenic variants. However, only 10 of these individuals were identified with a pathogenic variant associated with the criteria for which they met. Genetic testing that is limited to only those patients with genes associated with hereditary cancer syndromes may lead to exclusion of other potentially actionable genes, which may impair a patient’s ability to receive additional screening or preventative measures.

scholarly journals Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lucie G. Hallenstein ◽  
Carol Sorensen ◽  
Lorraine Hodgson ◽  
Shelly Wen ◽  
Justin Westhuyzen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Genetics ◽  
Eligibility Criteria ◽  
Pathogenic Variants ◽  
Genetics Services ◽  
Age Of Diagnosis ◽  
Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

scholarly journals The importance to update the guidelines for the use of genetic testing in noncancer patients in Brazil

2015 ◽  
Vol 49 (0) ◽  
Author(s):  
Tirzah Braz Petta Lajus
Keyword(s):  
Genetic Testing ◽  
Private Health Insurance ◽  
Breast Lesion ◽  
Private Insurance ◽  
Technical Note ◽  
Cancer Syndrome ◽  
History Of ◽  
National Regulatory Agency ◽  
Generation Sequencing ◽  
History Of Cancer

The Brazilian National Regulatory Agency for Private Health Insurance and Plans has recently published a technical note defining the criteria for the coverage of genetic testing to diagnose hereditary cancer. In this study we show the case of a patient with a breast lesion and an extensive history of cancer referred to a private service of genetic counseling. The patient met both criteria for hereditary breast and colorectal cancer syndrome screening. Her private insurance denied coverage for genetic testing because she lacks current or previous cancer diagnosis. After she appealed by lawsuit, the court was favorable and the test was performed using next-generation sequencing. A deletion of MLH1 exon 8 was found. We highlight the importance to offer genetic testing using multigene analysis for noncancer patients.

Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing

2021 ◽  
pp. 1-9
Author(s):  
Pelin Ercoskun ◽  
Cigdem Yuce Kahraman ◽  
Guller Ozkan ◽  
Abdulgani Tatar
Keyword(s):  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Genetics And Genomics ◽  
Cancer Syndromes ◽  
Generation Sequencing

A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in the <i>MUTYH</i>, <i>BRCA2</i>, and <i>CHEK2</i> genes. Nine novel pathogenic/likely pathogenic variants were identified in <i>BRCA1</i>, <i>BRCA2</i>, <i>GALNT12</i>, <i>ATM</i>, <i>MLH1</i>, <i>MSH2</i>, <i>APC</i>, and <i>KIT</i> genes. We obtained interesting and novel variants which could be related to hereditary cancer, and this study confirmed that NGS is an indispensable method for the risk assessment in cancer families.

Hereditary Diffuse Gastric Cancer: Approaches to Screening, Surveillance, and Treatment

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Nastazja Dagny Pilonis ◽  
Marc Tischkowitz ◽  
Rebecca C. Fitzgerald ◽  
Massimiliano di Pietro
Keyword(s):  
Gastric Cancer ◽  
Hereditary Diffuse Gastric Cancer ◽  
Prophylactic Surgery ◽  
Future Research ◽  
Annual Review ◽  
Publication Date ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Pathogenic Variants ◽  
History Of

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with a significant lifetime risk of diffuse gastric cancer (DGC), a malignancy characterized by late clinical presentation and poor prognosis, as well as lobular breast cancer. HDGC is linked to germline pathogenic variants in the E-cadherin gene ( CDH1) that are inherited in an autosomal dominant pattern; however, in many families with DGC clustering, no genetic cause has been identified. This review discusses key elements that allow risk assessment of potential inherited DGC susceptibility. We provide a practical overview of the recommendations for surveillance and treatment of individuals at risk and patients with early disease. The review also outlines future research avenues to improve our understanding of the genetic background and natural history of the disease, the endoscopic detection of early lesions, and the outcome of prophylactic surgery in young individuals. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

scholarly journals SDHB Associated Paraganglioma Syndrome in Africa – A Need for Greater Genetic Testing

2021 ◽  
Author(s):  
Nida Siddiqui ◽  
Faheem Seedat ◽  
Saajidah Bulbulia ◽  
Nompumelelo Z Mtshali ◽  
Adam Botha ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Germline Mutation ◽  
African Ancestry ◽  
Limited Data ◽  
Sdhb Mutation ◽  
Class V ◽  
Genes Encoding ◽  
History Of ◽  
Paraganglioma Syndrome ◽  
African Patients

Abstract A germline mutation is identified in almost 40% of Pheochromocytoma-Paraganglioma (PPGL) Syndromes. Genetic testing and counselling are essential for the management of index cases as well as pre-symptomatic identification and pre-emptive management of affected family members. Mutations in the genes encoding the mitochondrial enzyme succinate dehydrogenase (SDH) are well described in patients with hereditary PPGL. Amongst patients of African ancestry the prevalence, phenotype, germline mutation spectrum and penetrance of SDH mutations is poorly characterized. We describe a multifocal paraganglioma in a young African male with an underlying mis-sense SDHB mutation, with a history of three first-degree relatives who demised at young ages from suspected cardiovascular causes. The same SDHB mutation, Class V variant c.724C&gt;A p.(Arg242Ser), was detected in one of his asymptomatic siblings. As there is limited data describing hereditary PPGL syndromes in Africa this report of an SDHB associated PPGL is a notable contribution to the literature in this growing field. Due to the noteworthy clinical implications of PPGL mutations, it highlights the existing need for broader genetic screening amongst African patients with PPGL despite the limited healthcare resources available in this region.

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