Familial Cancer最新文献

{"title":"Report of the sixth meeting of the European Consortium 'Care for CMMRD' (C₄CMMRD), Paris, France, November 16th 2022.","authors":"Léa Guerrini-Rousseau, Richard Gallon, Marta Pineda, Laurence Brugières, Stéphanie Baert-Desurmont, Carole Corsini, Volodia Dangouloff-Ros, Mark A J Gorris, Christine Haberler, Pauline Hoarau, Marjolijn C Jongmans, Matthias Kloor, Jan Loeffen, Charlotte Rigaud, Julie Robbe, Roseline Vibert, Dilys Weijers, Katharina Wimmer, Chrystelle Colas","doi":"10.1007/s10689-024-00403-1","DOIUrl":"10.1007/s10689-024-00403-1","url":null,"abstract":"<p><p>Biallelic germline pathogenic variants in one of the four mismatch repair genes (MSH2, MSH6, MLH1 and PMS2) cause a very rare, highly penetrant, childhood-onset cancer syndrome, called constitutional mismatch repair deficiency (CMMRD). The European consortium \"Care for CMMRD\" (C4CMMRD) was founded in Paris in 2013 to facilitate international collaboration and improve our knowledge of this rare cancer predisposition syndrome. Following initial publications on diagnostic criteria and surveillance guidelines for CMMRD, several partners collaborating within the C4CMMRD consortium have worked on and published numerous CMMRD-related clinical and biological projects. Since its formation, the C4CMMRD consortium held meetings every 1-2 years (except in 2020 and 2021 due to the Covid 19 pandemic). The sixth C4CMMRD meeting was held in Paris in November 2022, and brought together 42 participants from nine countries involved in various fields of CMMRD healthcare. The aim was to update members on the latest results and developments from ongoing research, and to discuss and initiate new study proposals. As previously done for the fifth meeting of the C4CMMRD group, this report summarizes data presented at this meeting.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"447-457"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731059","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}

{"title":"A de novo germline pathogenic BRCA1 variant identified following an osteosarcoma pangenomic molecular analysis.","authors":"Adrien Mouren, Albain Chansavang, Nadim Hamzaoui, Arunya Srikaran, Pierre Laurent-Puig, Laetitia Marisa, Sixtine De Percin, Audrey Lupo, Frédérique Larousserie, Hélène Blons, Anais L'Haridon, Nelly Burnichon, Eric Pasmant, Camille Tlemsani","doi":"10.1007/s10689-024-00393-0","DOIUrl":"10.1007/s10689-024-00393-0","url":null,"abstract":"<p><p>De novo germline pathogenic variants (gPV) of the BReast CAncer 1 (BRCA1) gene are very rare. Only a few have been described up to date, usually in patients with a history of ovarian or breast cancer. Here, we report the first case of an incidental de novo BRCA1 germline pathogenic variant which was identified within the framework of the Plan France Médecine Génomique (PFMG) 2025 French national tumor sequencing program. The proband was a 29-year-old man diagnosed with metastatic osteosarcoma. Tumor whole exome sequencing identified a BRCA1 c.3756_3759del p.(Ser1253Argfs*10) pathogenic variant without loss-of-heterozygosity. A low genomic instability score and the absence of single base substitution signatures of homologous recombination deficiency suggested that the BRCA1 variant was not driver in the osteosarcoma tumorigenesis. Germline whole genome sequencing asserted the germline nature of this variant, with a 36% allele frequency, suggesting a mosaicism caused by a post-zygotic mutational event. The proband's family (parents and siblings) were not carriers of this variant confirming the de novo occurrence. Tumor sequencing programs like the French PFMG 2025 have been implemented worldwide and may help identify new gPV, including de novo variants.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"627-634"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065180","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}

{"title":"Detection of a major Lynch Syndrome-causing MLH1 founder variant in a large-scale genotyped cohort.","authors":"Lauri J Sipilä, Mervi Aavikko, Janne Ravantti, Samantha Martin, Teijo Kuopio, Laura Lahtinen, FinnGen, Päivi Peltomäki, Jukka-Pekka Mecklin, Lauri A Aaltonen, Toni T Seppälä","doi":"10.1007/s10689-024-00400-4","DOIUrl":"10.1007/s10689-024-00400-4","url":null,"abstract":"<p><p>Some 50% of Finnish Lynch Syndrome (LS) cases are caused by a founder variant in MLH1, in which the entire exon 16 has been lost due to an Alu-mediated recombination event. We piloted detecting the variant in FinnGen, a large genotyped cohort comprising approximately 10% of the current Finnish population, and validated the MLH1 founder variant status of identified individuals residing in the Central Finland Biobank catchment area. A consensus sequence flanking the deletion was identified in whole genome sequences of six LS individuals with the founder variant. Genotype data of 212,196 individuals was queried for regional matches to the consensus sequence. Enrichment of cancer and age at cancer onset was compared between matching and non-matching individuals. Variant status was validated for a subset of the identified individuals using a polymerase chain reaction assay. Allelic matches in a chosen target region was detected in 348 individuals, with 89 having a cancer diagnosis (Bonferroni-adjusted p-value = 1), 20 a familial cancer history (p-adj. < .001), with mean age of onset of cancer being 53.6 years (p-adj. = .002). Eighteen of potential variant carriers had been sampled by the Central Finland Biobank, of which four (22%) were validated as true variant carriers. The workflow we have employed identifies MLH1 exon 16 deletion variant carriers from population-wide SNP genotyping data. An alternative design will be sought to limit false positive findings. Large genotyped cohorts provide a potential resource for identification and prevention of hereditary cancer.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"647-652"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283411","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}

{"title":"Endoscopic indicators in patients with familial adenomatous polyposis undergoing duodenal resections - a nationwide Danish cohort study with long-term follow-up.","authors":"J G Karstensen, M D Wewer, S Bülow, Tvo Hansen, H Højen, A M Jelsig, T P Kuhlmann, J Burisch, H C Pommergaard","doi":"10.1007/s10689-024-00415-x","DOIUrl":"10.1007/s10689-024-00415-x","url":null,"abstract":"<p><strong>Background: </strong>Familial adenomatous polyposis (FAP) predisposes individuals to duodenal adenomas. This study describes the histopathological features of endoscopic and surgical specimens from the duodenum, as well as genotype-phenotype associations.</p><p><strong>Methods: </strong>All known FAP patients were included from the Danish Polyposis Register. FAP patients were defined as having more than 100 cumulative colorectal adenomas and/or having a known germline pathogenic variant in the APC gene. Endoscopic procedures, histopathology, and genetics were evaluated.</p><p><strong>Results: </strong>Of 500 FAP patients, 70.6% underwent esophagogastroduodenoscopy (EGD) at least once. Of these, 59.2% presented with detectable duodenal adenomas. The most severe morphology was tubular in 62.7% patients, tubulovillous in 25.4%, and villous in 12.0%, while the most severe dysplasia was low-grade in 67.5% patients, high-grade in 25.4%, and 6.7% had adenocarcinoma. In 6.2% of FAP patients, duodenal resection was recommended, including 29% with duodenal adenocarcinoma. The risk of duodenal surgery was 1.31 per 1,000 person-years (median age: 53 years). The predominant reason for surgery was extensive polyposis (67.7%). Of the patients who underwent duodenal resection, a median of six (IQR: 4-8) EGDs were performed within five years prior to surgery, but 67.6% and 83.9% never underwent a duodenal polypectomy or endoscopic mucosa resection, respectively. Of note, seventeen of 500 patients (3.4%) developed duodenal adenocarcinoma, of which 47% were advanced at diagnosis. Genetic evaluations revealed various pathogenic variants in the APC gene, with no strong genotype-phenotype association.</p><p><strong>Conclusions: </strong>The prevalence of duodenal adenomas and cancer in FAP warrants vigilant endoscopic surveillance. Nevertheless, the need for duodenal surgery persists and should together with endoscopic practice be monitored in national registers.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"607-615"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751448","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}

{"title":"Use and feasibility of a Lynch Syndrome predictive model for inherited colorectal and endometrial cancer in a low-middle income country.","authors":"Monica A Bissmeyer, Angel Velarde, Ana S Salazar, Abigail S Zamorano","doi":"10.1007/s10689-024-00422-y","DOIUrl":"10.1007/s10689-024-00422-y","url":null,"abstract":"<p><p>While universal tumor testing for Lynch Syndrome (LS) is recommended in all new diagnoses of colorectal cancer (CC) and endometrial cancer (EC), the cost and availability of this test in low-resource settings poses challenges. The PREdiction Model for gene Mutations (PREMM₅) is a clinical algorithm designed to assess the risk of an individual carrying estimates one's risk of carrying a LS mutation. This study aims to assess the feasibility of using PREMM₅ to screen for LS risk in Guatemala. This cross-sectional pilot study enrolled 50 patients with colorectal or endometrial cancer receiving treatment at LIGA-INCAN, a cancer hospital in Guatemala City, between June 2022-July 2022. Patients were contacted by phone and administered the PREMM₅ survey, followed by an additional feasibility questionnaire. Of the 50 participants, 62% of patients had a PREMM₅ predicted probability of ≥ 2.5%, the threshold above which genetic testing is recommended. Almost all patients found the survey easy to complete (98%), were able to easily recall personal (90%) and family (88%) medical history, understood its purpose (94%), and reported an interest in (96%) and ability to (98%) act on the results if applicable. Our study shows the role of the PREMM₅ as a feasible tool for identifying individuals at risk of carrying mutations associated with LS in this low-resource setting. By implementing the PREMM₅ model, high risk individuals can be identified early, enabling timely interventions and improving outcomes in this at-risk population.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"563-567"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344478","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}

{"title":"Somatic STK11 mosaicism in a Turkish patient with Peutz-Jeghers syndrome.","authors":"Mustafa Yilmaz, Ogun Bebek, Yavuzhan Colak, Ayberk Türkyılmaz","doi":"10.1007/s10689-024-00405-z","DOIUrl":"10.1007/s10689-024-00405-z","url":null,"abstract":"<p><p>Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder, caused by germline variants in the serine/threonine kinase 11 (STK11) gene. However, mosaic variants in STK11 gene have been rarely described. A 25-year-old woman diagnosed with PJS due to multiple hamartomatous polyps in the gastrointestinal tract was referred to our clinic. In the molecular diagnosis, the patient was evaluated using the STK11 gene sequence analysis and multiplex ligation-dependent probe amplification (MLPA) method, which suggested no pathogenic variant to account for the clinical picture. Given that the clinical findings of the patient were consistent with those of PJS, the raw data from next-generation sequencing (NGS) were re-examined for mosaicism which led to the detection of a novel mosaic c.920 + 1G > T variant in STK11 gene with a rate of 23% (1860x). Deep read-level NGS was performed on buccal mucosa and polyp samples to determine mosaicism levels in other tissues. Variant frequencies were 29% (710x) and 31% (1301x), respectively. Mosaicism should be considered in cases with clear clinical diagnostic criteria, such as PJS, where the pathogenic variant cannot be detected by sequence analysis and MLPA methods. Identification of mosaicism in these patients is very important as it can have an impact on patient follow-up and genetic counseling for relatives.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"641-645"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186327","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}

{"title":"Asymptomatic Bloom syndrome diagnosed by chance in a patient with breast cancer.","authors":"Evgeny Suspitsin, Darya Eliseyeva, Olga Chiryaeva, Evgeniya Belogubova, Svetlana Aleksakhina, Anna Sokolenko, Evgeny Imyanitov","doi":"10.1007/s10689-024-00420-0","DOIUrl":"10.1007/s10689-024-00420-0","url":null,"abstract":"<p><p>Bloom syndrome (BS) is a rare genetic disorder caused by biallelic inactivation of the BLM gene, which usually manifests in childhood by significant growth retardation, immune deficiency, characteristic skin lesions, cancer predisposition and other distinguishable disease features. To our knowledge, all prior instances of BS have been identified via intentional analysis of patients with clinical suspicion for this disease or DNA testing of members of affected pedigrees. We describe an incidental finding of BS, which occurred upon routine germline DNA analysis of consecutive breast cancer patients. The person with the biallelic pathogenic BLM c.1642C>T (p.Gln548Ter) variant remained clinically healthy for 38 years until she developed breast cancer. Detailed examination of this woman, which was carried out after the genetic diagnosis, revealed mild features of BS. A sister chromatid exchange (SCE) test confirmed the presence of this syndrome. The tumor exhibited triple-negative receptor status, a high proliferation rate, a low tumor mutation burden (TMB), and a moderate level of chromosomal instability (homologous recombination deficiency (HRD) score = 29). The patient showed normal tolerability to radiotherapy and several regimens of cytotoxic therapy. Thus, some BS patients may remain undiagnosed due to the mild phenotype of their disease. BLM should be incorporated in gene panels utilized for germline DNA testing of cancer patients.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"659-664"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139722","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}

{"title":"Metastatic disease after removal of a renal cell carcinoma smaller than 3 cm in a patient with Birt-Hogg-Dubé syndrome, a case report.","authors":"L van Riel, C M Kets, L P van Hest, F H Menko, B G Boerrigter, S M Franken, R M F Wolthuis, H J Dubbink, P J Zondervan, R J A van Moorselaar, A C Houweling, I van de Beek","doi":"10.1007/s10689-024-00408-w","DOIUrl":"10.1007/s10689-024-00408-w","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"579-582"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426634","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}

{"title":"The 17th International Meeting on Psychosocial Aspects of Hereditary Cancer (IMPAHC) : May 23-24, 2023 Rockville, Maryland, United States.","authors":"","doi":"10.1007/s10689-024-00396-x","DOIUrl":"10.1007/s10689-024-00396-x","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"675-702"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418519","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}

{"title":"Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.","authors":"Alice Youngs, Andrea Forman, Marisa Elms, Kelly Kohut, Min Theik Hlaing, John Short, Helen Hanson, Katie Snape","doi":"10.1007/s10689-024-00407-x","DOIUrl":"10.1007/s10689-024-00407-x","url":null,"abstract":"<p><p>Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement. Digital data from 4,044 cFHQS respondents over a three-year period was collected and interrogated with respect to the number and type of familial tumour diagnoses to enable service improvement and streamlining of referral pathways. 81% of colorectal and 71% of breast screening assessments were population- or moderate-risk. Most patients who completed cFHQS reported more than one diagnosis of cancer/tumour/polyps in their family. 2.5% of family history assessment patients had a second indication that required assessment that would have been missed if single tumour type assessment was undertaken. Implementation of an innovative, digital family history data collection pathway has allowed large scale interrogation of referral patterns and assessment outcomes to enable service development. The high volume of inappropriate referrals to Clinical Genetics for population and moderate risk patients highlighted the need for dedicated secondary care pathway provision for these patients. The use of cFHQS streamlined family history assessment allows for redistribution of resources to improve equity and access to genetic cancer risk assessment.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"591-598"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491484","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}