scholarly journals Using family history forms in pediatric oncology to identify patients for genetic assessment

2017 ◽  
Vol 24 (6) ◽  
pp. 441 ◽  
Author(s):  
A. Hamilton ◽  
E. Smith ◽  
J. Hamon ◽  
E. Tomiak ◽  
M. Bassal ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Pediatric Oncology ◽  
Small Sample ◽  
Cancer Predisposition ◽  
Candidate Gene Approach ◽  
Inherited Cancer ◽  
Cancer Predisposition Syndrome ◽  
Pediatric Cancer Patients ◽  
History Of

Objective We set out to identify and offer genetic testing to the 5%–10% of pediatric cancer patients who have been estimated to carry germline mutations in inherited cancer predisposition syndromes. Clinical genetic testing has become widely available, and thus in busy oncology clinics, tools are needed to identify patients who could benefit from a referral to genetics.Methods We studied the clinical utility of administering a family history form in the pediatric oncology long-term follow-up clinic to identify patients who might have an inherited cancer predisposition syndrome. Genetic testing involved primarily Sanger sequencing in clia (Clinical Laboratory Improvement Amendments)–certified laboratories.Results Of 57 patients who completed forms, 19 (33.3%) met criteria for referral to genetics. A significant family history of cancer was present for 4 patients, and 12 patients underwent genetic testing. Of 18 genetic tests ordered, none identified a pathogenic mutation, likely because of a small sample size and a candidate-gene approach to testing. Three families were also identified for further assessment based on a family history of breast cancer, with two of families having members eligible for BRCA1 and BRCA2 testing.Conclusions Genetic testing in pediatric oncology patients is important to guide the management of patients who have an inherited cancer predisposition syndrome and to identify other family members at risk when mutations are identified. When no mutations are identified, that information is often reassuring to families who are worried about siblings. However, in the absence of an identified genetic cause in a patient, some uncertainty remains.

scholarly journals Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness

2020 ◽  
Author(s):  
Leann A Lovejoy ◽  
Clesson E Turner ◽  
Craig D Shriver ◽  
Rachel E Ellsworth
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Predisposition ◽  
Clinical Genetic ◽  
High Risk Women ◽  
Clinical Genetic Testing ◽  
Pathogenic Mutations ◽  
History Of ◽  
Risk Reducing

Abstract Background The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer. Breast cancer is, however, the most common cancer in ADS and may have a significant effect on troop readiness with lengthy absence during treatment and inability to return to duty after the treatment. The identification of unaffected ADS who carry germline mutations in cancer predisposition genes (“previvors”) would provide the opportunity to prevent or detect cancer at an early stage, thus minimizing effects on troop readiness. In this study, we determined (1) how many high-risk ADS without cancer pursued genetic testing, (2) how many previvors employed risk-reducing strategies, and (3) the number of undiagnosed previvors within an ADS population. Methods The Clinical Breast Care Project (protocol WRNMMC IRB #20704) database of the Murtha Cancer Center/Walter Reed National Military Medical Center was queried to identify all ADS with no current or previous history of cancer. Classification as high genetic risk was calculated using National Comprehensive Cancer Network 2019 guidelines for genetic testing for breast, ovary, colon, and gastric cancer. The history of clinical genetic testing and risk-reducing strategies was extracted from the database. Genomic DNA from ADS with blood specimens available for research purposes were subjected to next-generation sequencing technologies using a cancer predisposition gene panel. Results Of the 336 cancer-free ADS enrolled in the Clinical Breast Care Project, 77 had a family history that met National Comprehensive Cancer Network criteria for genetic testing for BRCA1/2 and 2 had a family history of colon cancer meeting the criteria for genetic testing for Lynch syndrome. Of the 28 (35%) high-risk women who underwent clinical genetic testing, 11 had pathogenic mutations in the breast cancer genes BRCA1 (n = 5), BRCA2 (n = 5), or CHEK2 (n = 1). Five of the six ADS who had a relative with a known pathogenic mutation were carriers of the tested mutation. All of the women who had pathogenic mutations detected through clinical genetic testing underwent prophylactic double mastectomy, and three also had risk-reducing salpingo-oophorectomy. Two (6%) of the 33 high-risk ADS tested only in the research setting had a family history of breast/ovarian cancer and carried pathogenic mutations: one carried a BRCA2 mutation, whereas the other carried a mutation in the colon cancer predisposition gene PMS2. No mutations were detected in the 177 low-risk women tested in the research setting. Discussion Within this unaffected cohort of ADS, 23% were classified as high risk. Although all of the previvors engaged in risk-reduction strategies, only one-third of the high-risk women sought genetic testing. These data suggest that detailed family histories of cancer should be collected in ADS and genetic testing should be encouraged in those at high risk. The identification of previvors and concomitant use of risk-reduction strategies may improve health in the ADS and optimize military readiness by decreasing cancer incidence.

scholarly journals DICER1 Mutations in the Era of Expanding Integrative Clinical Sequencing in Pediatric Oncology

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kelly M. Bailey ◽  
Michelle F. Jacobs ◽  
Bailey Anderson ◽  
Raja Rabah ◽  
Yi-Mi Wu ◽  
...  
Keyword(s):  
Pediatric Oncology ◽  
Cancer Predisposition ◽  
Response To Therapy ◽  
Sequencing Data ◽  
Clinical Sequencing ◽  
Inherited Cancer ◽  
Cancer Predisposition Syndrome ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Dicer1 Syndrome

PURPOSE DICER1 syndrome is a recently described inherited cancer predisposition syndrome caused by pathogenic variants in DICER1. With the recent increase in integrative clinical sequencing for pediatric patients with cancer, our understanding of the DICER1 syndrome continues to evolve, as new and rare pathogenic variants are reported. As the frequency of integrative clinical sequencing increases, discussions regarding challenges encountered in the interpretation of sequencing results are essential to continue to advance the field of cancer predisposition. The purpose of this work was to identify patients with somatic and/or germline DICER1 variants in our patient population and to discuss sequencing interpretation and the clinical recommendations that result from the integrative clinical sequencing results. METHODS Patients were enrolled in the PEDS-MIONCOSEQ study. This integrative clinical sequencing study includes paired tumor/normal whole-exome sequencing and tumor transcriptome sequencing. Patients identified as having DICER1 variants were included. RESULTS We report a DICER1 variant of unknown clinical significance in a patient with a highly unusual response to therapy. Two patients had diagnoses clarified once the integrative clinical sequencing revealing a DICER1 variant was available. We also discovered a patient with low-level DICER1 mosaicism and the challenges encountered in the sequencing interpretation for this patient. In addition to the sequencing data and result interpretation, this work also highlights testing and screening recommendations made to patients with DICER1 variants and their families on the basis of these results. CONCLUSION This work serves to extend the DICER1 phenotype and advance the utility of clinical integrative sequencing in the fields of pediatric oncology and cancer genetic predisposition.

scholarly journals Maxillary mesenchymal chondrosarcoma leading to a diagnosis of Li-Fraumeni syndrome

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Eduardo Ventura ◽  
Sílvia Dionísio ◽  
Ângela Ferreira ◽  
Rute Saleiro ◽  
Hugo Marques ◽  
...  
Keyword(s):  
Family History ◽  
Adjuvant Chemotherapy ◽  
Uterine Cancer ◽  
Surgical Excision ◽  
Cancer Predisposition ◽  
Mesenchymal Chondrosarcoma ◽  
Li Fraumeni Syndrome ◽  
Cancer Predisposition Syndrome ◽  
History Of ◽  
Li Fraumeni

Abstract Mesenchymal chondrosarcoma (MCS) is a rare histological variant of chondrosarcoma, with aggressive behaviour. Due to the unique nature of this disease, management strategies are not well established. Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome with a wide tumour spectrum, associated with TP53 germline mutations. We report a case of MCS of the maxilla, treated with surgical excision and adjuvant chemotherapy, in a patient with a past medical history of choroid plexus papilloma and a family history of early age first-degree cervical uterine cancer, that led to the clinical suspicion of a cancer predisposition syndrome and the subsequent diagnosis of LFS. This is the first MCS described in a LFS case. It demonstrates that adjuvant chemotherapy should be considered, in conjunction with surgical excision, in MCS and that cancer predisposition syndromes should be suspected in patients with multiple neoplasms and a strong family history of cancer.

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

scholarly journals Serial Observations and Mutational Analysis of an Adoptee with Family History of Hypertrophic Cardiomyopathy

2010 ◽  
Vol 2010 ◽  
pp. 1-4
Author(s):  
Bronwyn Harris ◽  
Jean P. Pfotenhauer ◽  
Cheri A. Silverstein ◽  
Larry W. Markham ◽  
Kim Schafer ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Family History ◽  
Mutational Analysis ◽  
Clinical Findings ◽  
Dominant Mode ◽  
Natural Mother ◽  
History Of ◽  
In Cis ◽  
Inherited Cardiac Disease

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease with an autosomal dominant mode of transmission. Comprehensive genetic screening of several genes frequently found mutated in HCM is recommended for first-degree relatives of HCM patients. Genetic testing provides the means to identify those at risk of developing HCM and to institute measures to prevent sudden cardiac death (SCD). Here, we present an adoptee whose natural mother and maternal relatives were known be afflicted with HCM and SCD. The proband was followed closely from age 6 to 17 years, revealing a natural history of the progression of clinical findings associated with HCM. Genetic testing of the proband and her natural mother, who is affected by HCM, revealed that they were heterozygous for both the R719Q and T1513S variants in the cardiac beta-myosin heavy chain (MYH7) gene. The proband's ominous family history indicates that the combination of the R719Q and T1513S variantsin cismay be a “malignant” variant that imparts a poor prognosis in terms of the disease progression and SCD risk.

Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Stephanie M Ware ◽  
Steven E Lipshultz ◽  
Steven D Colan ◽  
Ling Shi ◽  
Charles E Canter ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Whole Exome ◽  
Pediatric Cardiomyopathy ◽  
History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

scholarly journals Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 169
Author(s):  
Matsubayashi ◽  
Kiyozumi ◽  
Ishiwatari ◽  
Uesaka ◽  
Kikuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Early Stage ◽  
Developed Countries ◽  
Familial Pancreatic Cancer ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Clinicopathological Findings ◽  
History Of ◽  
Cancer Syndromes

A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.

scholarly journals Motivation to Pursue Genetic Testing in Individuals with a Personal or Family History of Cardiac Events or Sudden Cardiac Death

2014 ◽  
Vol 23 (5) ◽  
pp. 849-859 ◽  
Author(s):  
Kathleen E. Erskine ◽  
Nadia Z. Hidayatallah ◽  
Christine A. Walsh ◽  
Thomas V. McDonald ◽  
Lilian Cohen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Cardiac Events ◽  
History Of

Genetic testing in young women with breast cancer: Results from a web-based survey

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21093-21093
Author(s):  
J. A. Shin ◽  
S. Gelber ◽  
J. Garber ◽  
R. Rosenberg ◽  
M. Przypyszny ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Young Women ◽  
College Education ◽  
Web Based ◽  
Increased Risk ◽  
History Of

21093 Background: Young women with breast cancer have an increased risk of harboring a BRCA1/2 mutation. The frequency of genetic testing in this population is not well described. We evaluated the reported frequency and factors associated with genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an international advocacy group for young women with breast cancer. Methods: Items regarding family history and genetic testing were included in a large web-based survey addressing quality of life and fertility issues for young women with breast cancer. All YSC members were invited by email in March 2003 (N= 1,703 women) to participate in this cross-sectional survey. Results: 657 women completed the on-line survey; 622 were eligible for this analysis (age <40, no metastatic or recurrent disease). Mean age at breast cancer diagnosis was 33 years; mean age when surveyed 35.5 years. Stages included: 0 (10%), I (27%), II (49%), III (12%), missing (3%). 90% of women were white; 64% married; 49% with children; 78% had at least a college education; 42% of women reported a 1st or 2nd degree relative with breast or ovarian cancer, and 13% considered themselves high-risk for harboring a genetic mutation at the time of diagnosis. At the time of the survey, 23% of women had undergone genetic testing, and 26% of those tested reported that a mutation was found. In a multivariate model, women who were younger (age 36–40 vs. age =30, O.R. 2.26, p=0.004), more educated (< college vs. > college education, O.R. 2.62, p=0.0009), had a family history of breast or ovarian cancer (O.R. 3.15, p<0.0001), and had had a mastectomy (O.R. 1.99, p=0.001) were more likely to have undergone genetic testing. Non-significant covariates included: age at survey, stage, time since diagnosis, race, marital status, employment, finances, insurance, number of children, comorbidities, baseline anxiety and depression, and fear of recurrence. Conclusion: The majority of women diagnosed with breast cancer age 40 and younger do not undergo genetic testing. Younger, more educated women with a family history of breast or ovarian cancer are more likely to get tested. Further research to define the appropriateness of genetic testing in this relatively high-risk population is warranted. No significant financial relationships to disclose.

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