Familial Cancer最新文献_第10页

Germline whole genome sequencing in adults with multiple primary tumors. 成人多原发性肿瘤种系全基因组测序。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2023-07-22 DOI: 10.1007/s10689-023-00343-2

Yiming Wang, Qiliang Ding, Stephenie Prokopec, Kirsten M Farncombe, Jeffrey Bruce, Selina Casalino, Jeanna McCuaig, Marta Szybowska, Kalene van Engelen, Jordan Lerner-Ellis, Trevor J Pugh, Raymond H Kim

{"title":"Germline whole genome sequencing in adults with multiple primary tumors.","authors":"Yiming Wang, Qiliang Ding, Stephenie Prokopec, Kirsten M Farncombe, Jeffrey Bruce, Selina Casalino, Jeanna McCuaig, Marta Szybowska, Kalene van Engelen, Jordan Lerner-Ellis, Trevor J Pugh, Raymond H Kim","doi":"10.1007/s10689-023-00343-2","DOIUrl":"10.1007/s10689-023-00343-2","url":null,"abstract":"Multiple primary tumors (MPTs) are a harbinger of hereditary cancer syndromes. Affected individuals often fit genetic testing criteria for a number of hereditary cancer genes and undergo multigene panel testing. Other genomic testing options, such as whole exome (WES) and whole genome sequencing (WGS) are available, but the utility of these genomic approaches as a second-tier test for those with uninformative multigene panel testing has not been explored. Here, we report our germline sequencing results from WGS in 9 patients with MPTs who had non-informative multigene panel testing. Following germline WGS, sequence (agnostic or 735 selected genes) and copy number variant (CNV) analysis was performed according to the American College of Medical Genetics (ACMG) standards and guidelines for interpreting sequence variants and reporting CNVs. In this cohort, WGS, as a second-tier test, did not identify additional pathogenic or likely pathogenic variants in cancer predisposition genes. Although we identified a CHEK2 likely pathogenic variant and a MUTYH pathogenic variant, both were previously identified in the multigene panels and were not explanatory for the presented type of tumors. CNV analysis also failed to identify any pathogenic or likely pathogenic variants in cancer predisposition genes. In summary, after multigene panel testing, WGS did not reveal any additional pathogenic variants in patients with MPTs. Our study, based on a small cohort of patients with MPT, suggests that germline gene panel testing may be sufficient to investigate these cases. Future studies with larger sample sizes may further elucidate the additional utility of WGS in MPTs.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"513-520"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9853748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Balancing the burden and benefits of colonoscopy in Lynch Syndrome. 平衡林奇综合征结肠镜检查的负担和益处。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2023-09-15 DOI: 10.1007/s10689-023-00347-y

Finlay Macrae

引用次数: 0

Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1. 影响1型神经纤维瘤病年轻女性乳腺筛查放射学解释的临床和影像学因素。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2023-06-19 DOI: 10.1007/s10689-023-00340-5

Mathilda Wilding, Jane Fleming, Katrina Moore, Ashley Crook, Ranjani Reddy, Sarah Choi, Timothy E Schlub, Michael Field, Lavvina Thiyagarajan, Jeff Thompson, Yemima Berman

{"title":"Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.","authors":"Mathilda Wilding, Jane Fleming, Katrina Moore, Ashley Crook, Ranjani Reddy, Sarah Choi, Timothy E Schlub, Michael Field, Lavvina Thiyagarajan, Jeff Thompson, Yemima Berman","doi":"10.1007/s10689-023-00340-5","DOIUrl":"10.1007/s10689-023-00340-5","url":null,"abstract":"Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"499-511"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unusual phenotypes in patients with a pathogenic germline variant in DICER1. DICER1致病性种系变异患者的异常表型。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2021-07-31 DOI: 10.1007/s10689-021-00271-z

Kateryna Venger, Miriam Elbracht, Julia Carlens, Peter Deutz, Felix Zeppernick, Lisa Lassay, Christian Kratz, Martin Zenker, Jung Kim, Douglas R Stewart, Ilse Wieland, Kris Ann P Schultz, Nicolaus Schwerk, Ingo Kurth, Udo Kontny

{"title":"Unusual phenotypes in patients with a pathogenic germline variant in DICER1.","authors":"Kateryna Venger, Miriam Elbracht, Julia Carlens, Peter Deutz, Felix Zeppernick, Lisa Lassay, Christian Kratz, Martin Zenker, Jung Kim, Douglas R Stewart, Ilse Wieland, Kris Ann P Schultz, Nicolaus Schwerk, Ingo Kurth, Udo Kontny","doi":"10.1007/s10689-021-00271-z","DOIUrl":"10.1007/s10689-021-00271-z","url":null,"abstract":"Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"475-480"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10689-021-00271-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam. 遗传性结直肠癌癌症综合征的患病率和遗传谱，提高癌症风险意识的必要性，以及越南的家庭级联检测。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2023-07-30 DOI: 10.1007/s10689-023-00344-1

Huu-Thinh Nguyen, Y-Thanh Lu, Duc-Huy Tran, Ba-Linh Tieu, Kien-Trung Le, Truong-Vinh Ngoc Pham, Thanh-Thuy Thi Do, Dinh-Kiet Truong, Hoa Giang, Hung-Sang Tang

{"title":"Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam.","authors":"Huu-Thinh Nguyen, Y-Thanh Lu, Duc-Huy Tran, Ba-Linh Tieu, Kien-Trung Le, Truong-Vinh Ngoc Pham, Thanh-Thuy Thi Do, Dinh-Kiet Truong, Hoa Giang, Hung-Sang Tang","doi":"10.1007/s10689-023-00344-1","DOIUrl":"10.1007/s10689-023-00344-1","url":null,"abstract":"In Vietnam, colorectal cancer is one of the top diagnosed cancers, with 5-10% originating from inherited mutations. This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers' awareness, and also investigate the barriers in familial testing. Genetic test reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed and reported. Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. 44% of cases further undertook cancer screening tests, and 48% of cases' families had uptake genetic testing. The biggest barrier of familial members for not taking genetic test was psychological reasons (fear, not being interested, or not feeling necessary). This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support. Also, study has suggested the needs of an innovative genetic testing process focusing on the quality of pre-and post-test consultancy, an increase in follow-ups, and the change in policy for permission of contacting relatives directly to improve the rate of cascade testing and proactive cancer screening.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"449-458"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma. 富马酸水合酶新变体FHc.199T的深层生物信息学表征 > G（p.Tyr67Asp）在遗传性平滑肌瘤病和肾细胞癌中的作用。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-10-01 Epub Date: 2023-06-15 DOI: 10.1007/s10689-023-00335-2

Anisse Chami, Thalía Rodrigues de Souza Zózimo, Thamiris Matias Alves, Carolina Guimarães Ramos Matosinho, Cleydson Santos, Marcela Mattos Simões, Walter Luiz Ribeiro Cabral, Bernardo Ferreira de Paula Ricardo, Agnaldo Lopes da Silva Filho, Maria Raquel Santos Carvalho, Letícia da Conceição Braga

{"title":"In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.","authors":"Anisse Chami, Thalía Rodrigues de Souza Zózimo, Thamiris Matias Alves, Carolina Guimarães Ramos Matosinho, Cleydson Santos, Marcela Mattos Simões, Walter Luiz Ribeiro Cabral, Bernardo Ferreira de Paula Ricardo, Agnaldo Lopes da Silva Filho, Maria Raquel Santos Carvalho, Letícia da Conceição Braga","doi":"10.1007/s10689-023-00335-2","DOIUrl":"10.1007/s10689-023-00335-2","url":null,"abstract":"Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to \"likely pathogenic\". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"481-486"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hereditary acute myeloid leukemia associated with C-terminal CEBPA germline variants. 与 C 端 CEBPA 基因变异有关的遗传性急性髓性白血病。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-07-01 Epub Date: 2023-03-06 DOI: 10.1007/s10689-023-00329-0

Amye M Harrigan, Amy M Trottier

引用次数: 0

Ninth International Symposium on Hereditary Breast and Ovarian Cancer : May 2-5, 2023 - Centre Mont-Royal, Montréal, Québec, Canada. 第九届遗传性乳腺癌和卵巢癌国际研讨会:2023年5月2-5日，加拿大，蒙特利尔皇家中心。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-07-01 DOI: 10.1007/s10689-023-00332-5

引用次数: 0

Heritable methylation marks associated with prostate cancer risk. 遗传性甲基化标记与前列腺癌风险有关。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-07-01 Epub Date: 2023-01-28 DOI: 10.1007/s10689-022-00325-w

James G Dowty, Chenglong Yu, Mahnaz Hosseinpour, Jihoon Eric Joo, Ee Ming Wong, Tu Nguyen-Dumont, Joseph Rosenbluh, Graham G Giles, Roger L Milne, Robert J MacInnis, Pierre-Antoine Dugué, Melissa C Southey

{"title":"Heritable methylation marks associated with prostate cancer risk.","authors":"James G Dowty, Chenglong Yu, Mahnaz Hosseinpour, Jihoon Eric Joo, Ee Ming Wong, Tu Nguyen-Dumont, Joseph Rosenbluh, Graham G Giles, Roger L Milne, Robert J MacInnis, Pierre-Antoine Dugué, Melissa C Southey","doi":"10.1007/s10689-022-00325-w","DOIUrl":"10.1007/s10689-022-00325-w","url":null,"abstract":"DNA methylation marks that are inherited from parents to offspring are known to play a role in cancer risk and could explain part of the familial risk for cancer. We therefore conducted a genome-wide search for heritable methylation marks associated with prostate cancer risk. Peripheral blood DNA methylation was measured for 133 of the 469 members of 25 multiple-case prostate cancer families, using the EPIC array. We used these families to systematically search the genome for methylation marks with Mendelian patterns of inheritance, then we tested the 1,000 most heritable marks for association with prostate cancer risk. After correcting for multiple testing, 41 heritable methylation marks were associated with prostate cancer risk. Separate analyses, based on 869 incident cases and 869 controls from a prospective cohort study, showed that 9 of these marks near the metastable epiallele VTRNA2-1 were also nominally associated with aggressive prostate cancer risk in the population.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"22 3","pages":"313-317"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perspectives on the implications of carrying putative pathogenic variants in the medulloblastoma predisposition genes ELP1 and GPR161. 透视髓母细胞瘤易感基因 ELP1 和 GPR161 潜在致病变体的影响。

IF 2.2 4区医学

Familial Cancer Pub Date : 2023-07-01 Epub Date: 2023-03-24 DOI: 10.1007/s10689-023-00330-7

Miriam J Smith, Emma R Woodward, D Gareth Evans

{"title":"Perspectives on the implications of carrying putative pathogenic variants in the medulloblastoma predisposition genes ELP1 and GPR161.","authors":"Miriam J Smith, Emma R Woodward, D Gareth Evans","doi":"10.1007/s10689-023-00330-7","DOIUrl":"10.1007/s10689-023-00330-7","url":null,"abstract":"Recent genetic sequencing studies in large series' of predominantly childhood medulloblastoma have implicated loss-of-function, predominantly truncating, variants in the ELP1 and GPR161 genes in causation of the MBSHH subtype specifically. The latter association, along with a report of an index case with some features of Gorlin syndrome has led to speculation that GPR161 may also cause Gorlin syndrome. We show that these genes are associated with relatively low absolute risks of medulloblastoma from extrapolating lifetime risks in the general population and odds ratios from the population database gnomAD. The projected risks are around 1 in 270-430 for ELP1 and 1 in 1600-2500 for GPR161. These risks do not suggest the need for MRI screening in infants with ELP1 or GPR161 variants as this is not currently recommended for PTCH1 where the risks are equivalent or higher. We also screened 27 PTCH1/SUFU pathogenic variant-negative patients with Gorlin syndrome for GPR161 and found no suspicious variants. Given the population frequencies of 0.0962% for GPR161 and 0.0687% for ELP1, neither of these genes can be a cause of Gorlin syndrome with an unexplained population frequency far lower at 0.0021%.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"22 3","pages":"341-344"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0