Familial Cancer最新文献_第3页

Hereditary breast cancer beyond BRCA: clinicopathological characteristics and long-term outcomes. BRCA以外的遗传性乳腺癌：临床病理特征和长期预后。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-06-12 DOI: 10.1007/s10689-025-00478-4

Kwinten Dejaegher, Ines Nevelsteen, Sileny Han, Jelle Verhoeven, Hans Wildiers, Kevin Punie

{"title":"Hereditary breast cancer beyond BRCA: clinicopathological characteristics and long-term outcomes.","authors":"Kwinten Dejaegher, Ines Nevelsteen, Sileny Han, Jelle Verhoeven, Hans Wildiers, Kevin Punie","doi":"10.1007/s10689-025-00478-4","DOIUrl":"10.1007/s10689-025-00478-4","url":null,"abstract":"Limited data exist on hereditary breast cancer characteristics and treatment driven by germline mutations beyond BRCA. Our primary aim is to describe the tumour and patient characteristics, treatment patterns and outcomes in patients with non-BRCA hereditary breast cancer with a focus on CHEK2, ATM, PALB2 and TP53 variants. This is a retrospective single centre hospital-based cohort study of adult patients with a known (likely) pathogenic germline mutation and breast cancer diagnosis in UZ Leuven before April 2022. Data collection included baseline demographics, breast cancer characteristics, treatment patterns and disease outcome variables. Cohorts of patients with variants in different genes will be compared. We retrieved 185 patients with variants in ATM (N = 40), CHEK2 (N = 114), PALB2 (N = 8) and TP53 (N = 23). Median age was significantly lower in the TP53 group (36 years, p = 0.001). Only estrogen receptor (ER) status (p = 0.005) and breast cancer subtype (p < 0.001) differed significantly across the defined gene cohorts. HER2-positive disease was more frequent in the TP53 subgroup (59.1%, p < 0.001). Neoadjuvant chemotherapy was more commonly administered in the PALB2 and TP53 cohorts (p = 0.011). Univariate and multivariate survival analysis by gene cohort showed no significant difference in survival outcomes. In our series, we confirm that TP53 carriers are younger at breast cancer diagnosis and have more often HER2-positive breast cancer. Triple-negative breast cancer is more frequent in the PALB2 carriers, while ER-positivity is most common in ATM and CHEK2 carriers. Survival outcomes were similar across different gene cohorts in this study.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"54"},"PeriodicalIF":1.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274615","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

Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality. 重新定义家族性腺瘤性息肉病：竞争、合作和单克隆之路。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-06-01 DOI: 10.1007/s10689-025-00479-3

Sylvain Ferrandon, Matthew F Kalady, Sanne M van Neerven

{"title":"Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality.","authors":"Sylvain Ferrandon, Matthew F Kalady, Sanne M van Neerven","doi":"10.1007/s10689-025-00479-3","DOIUrl":"10.1007/s10689-025-00479-3","url":null,"abstract":"Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome characterized by germline mutations in the APC gene that result in the development of hundreds of premalignant adenomas throughout the colon and rectum. Prophylactic surgery remains the primary intervention strategy, as there are currently no pharmacological treatment options for FAP patients. Previous therapeutic approaches have predominantly focused on reducing polyp size rather than preventing their initiation, thereby missing a key opportunity for early intervention. Crucially, to effectively target the earliest stages of tumour development requires a deeper understanding of the molecular mechanisms underlying adenoma formation. In this review, we evaluate the latest models and methods employed to investigate the origin of FAP adenomas. We describe how mutant cells expand from their initial emergence within the intestinal epithelium and how they compete with normal cells within intestinal crypts. In addition, we discuss how multiple mutant crypts cooperate to collectively form polyclonal adenomas, and how these polyclonal lesions gradually transition towards monoclonality as adenomas progress towards colorectal cancer. Finally, we highlight how these insights inform the development of targeted cancer prevention strategies for individuals with FAP.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"52"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198579","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

Familial adenomatous polyposis: non-surgical management of large bowel disease: endoscopic and chemoprevention strategies. 家族性腺瘤性息肉病：大肠疾病的非手术治疗：内镜和化学预防策略。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-06-01 DOI: 10.1007/s10689-025-00480-w

Maria Daca-Álvarez, Andrew Latchford, Maria Pellisé, Francesc Balaguer

引用次数: 0

Strategic Plan of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC): A practical roadmap to move the hereditary gastrointestinal cancer field forward. 美洲遗传性胃肠癌协作组战略计划（CGA-IGC）：推动遗传性胃肠癌领域向前发展的实用路线图。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-06-01 DOI: 10.1007/s10689-025-00473-9

Bryson W Katona, Peter P Stanich, Anu Chittenden, Michael J Hall, Gregory E Idos, Cathryn Koptiuch, Alicia Latham, Rachel Pearlman, Aparajita Singh, Elana Levinson, Beth Dudley

引用次数: 0

5'UTR gene regions in germline DNA sequencing panels: lessons from the analysis of breast and ovarian cancer patients of Tatar and Bashkir ethnic origin. 生殖系DNA测序面板中的5'UTR基因区域：来自塔塔尔和巴什基尔族乳腺癌和卵巢癌患者分析的教训。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-05-26 DOI: 10.1007/s10689-025-00477-5

Anna P Sokolenko, Aigul R Venina, Alexandr A Romanko, Evgenia V Belogubova, Alexandr V Sultanbayev, Vadim E Askarov, Gulnara K Mukhamediarova, Elvina Kh Bakaeva, Maria V Syomina, Tatiana Yu Velyukhova, Elena V Preobrazhenskaya, Alexandr V Togo, Evgeny N Imyanitov

{"title":"5'UTR gene regions in germline DNA sequencing panels: lessons from the analysis of breast and ovarian cancer patients of Tatar and Bashkir ethnic origin.","authors":"Anna P Sokolenko, Aigul R Venina, Alexandr A Romanko, Evgenia V Belogubova, Alexandr V Sultanbayev, Vadim E Askarov, Gulnara K Mukhamediarova, Elvina Kh Bakaeva, Maria V Syomina, Tatiana Yu Velyukhova, Elena V Preobrazhenskaya, Alexandr V Togo, Evgeny N Imyanitov","doi":"10.1007/s10689-025-00477-5","DOIUrl":"10.1007/s10689-025-00477-5","url":null,"abstract":"Background: Tatars and Bashkirs are large and closely related ethnic communities that reside in the territory of the Russian Federation but have managed to preserve their national identity through the course of history.Methods: This study included 446 Tatars, 53 Bashkirs, and 26 women of mixed Tatar-Bashkir ethnicity. Germline DNA analysis was performed for 349 breast cancer (BC) patients with clinical features of hereditary disease (family history, or young onset (</= 50 years), or BC bilaterality, or triple-negative receptor status (lack of expression of ER, PgR, and HER2) and 176 subjects with high-grade serous ovarian cancer (HGSOC).Results: BRCA1 pathogenic variants (PVs) were detected in 63 women; surprisingly, five Slavic founder alleles accounted for 30 (48%) of the BRCA1 PVs. The genuine Tatar BRCA1 allele, c.5161C > T, was observed in 11 subjects. Among 27 women with BRCA2 PVs, six and five women were carriers of the c.-39-1_-39del and c.468dup variants, respectively. The loss-of-heterozygosity (LOH) test confirmed the pathogenic nature of the c.-39-1_-39del [rs758732038] allele, which is located in the 5'UTR of BRCA2. Analysis of other BC-associated genes revealed single instances of PVs affecting PALB2, TP53, ATM, RAD51, and RAD51D genes.Conclusion: Tatars and Bashkirs, which are ethnically and religiously separated from Russians, carry an unexpectedly high proportion of Slavic BRCA1/2 founder alleles. The identification of recurrent Tatar/Bashkir BRCA2 pathogenic 5'UTR variant c.-39-1_-39del calls for a systematic analysis of regulatory regions of cancer-predisposing genes in patients with missing heritability.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"50"},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149806","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

Detection rates of multigene panel and exome testing in patients with previous negative BRCA1/2 results. 既往BRCA1/2阴性患者的多基因面板和外显子组检测检出率

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-05-26 DOI: 10.1007/s10689-025-00471-x

Jewel L Wasson, Trinity N Sprague, Darcy L Thull, Maureen May, Kathleen E Vitale, Shenin A Sanoba, Alexander N Yatsenko, Daniel Bellissimo, Phuong L Mai

{"title":"Detection rates of multigene panel and exome testing in patients with previous negative BRCA1/2 results.","authors":"Jewel L Wasson, Trinity N Sprague, Darcy L Thull, Maureen May, Kathleen E Vitale, Shenin A Sanoba, Alexander N Yatsenko, Daniel Bellissimo, Phuong L Mai","doi":"10.1007/s10689-025-00471-x","DOIUrl":"10.1007/s10689-025-00471-x","url":null,"abstract":"Since panel genetic testing has become widely available, national guidelines recommend that individuals who previously underwent BRCA1/2-only testing should undergo updated testing to include other hereditary breast and ovarian cancer predisposition genes. Our study assessed the yield of additional hereditary cancer predisposition testing in patients who previously underwent negative BRCA1/2 testing. Additionally, our study included a small pilot to evaluate whole exome sequencing in patients with a strong family history. Patients enrolled in a registry study who previously underwent negative BRCA1/2 testing were included and stratified into three categories based on personal and family cancer history-strongly suggestive, moderately suggestive, and possibly suggestive. Updated testing with a 36-gene pan-cancer panel was performed on most participants. A selected set of participants had whole exome sequencing. Patients with a pathogenic variant identified were offered clinical confirmatory testing. Rates of positive test results were compared among the three groups. Clinically relevant pathogenic variants in non-BRCA1/2 genes from the 36-gene panel test were identified in 8.1% of participants, most commonly in PALB2 (1.9%), ATM (1.2%), and MSH6 (1.2%). Positive findings were more common in patients with strongly suggestive history, but the differences were not statistically significant. Exome testing in individuals with a strongly suggestive personal and family history did not yield novel findings. Our findings aligned with previous studies and support the use of expanded gene panel testing in all patients meeting testing criteria who previously underwent negative BRCA1/2 testing. Our small pilot whole exome sequencing did not identify any novel finding.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"48"},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141887","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

Screening of biobank SNP-array genotyping data to detect Lynch syndrome predisposing MLH1 copy number variants. 筛选biobank snp阵列基因分型数据，检测Lynch综合征易感MLH1拷贝数变异。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-05-26 DOI: 10.1007/s10689-025-00476-6

Kimmo Ala-Kulju, Olli Carpén, Maarit Lappalainen, Minja Pehrsson

{"title":"Screening of biobank SNP-array genotyping data to detect Lynch syndrome predisposing MLH1 copy number variants.","authors":"Kimmo Ala-Kulju, Olli Carpén, Maarit Lappalainen, Minja Pehrsson","doi":"10.1007/s10689-025-00476-6","DOIUrl":"10.1007/s10689-025-00476-6","url":null,"abstract":"Efficient use of genetic biobank data in support of clinical care would enhance the adoption of personalized medicine. Identification of carriers of medically actionable variants that predispose to cancer enables intensified screening and follow-up to decrease disease risk. Pathogenic variants of the MLH1 gene cause Lynch syndrome with a significant risk of developing cancer. Here, we introduce a novel approach for the large-scale screening of biobank SNP-array-based genotyping data to analyze copy-number variants (CNVs). With the method developed, we analyzed the Helsinki Biobank cohort of 121 073 samples and identified 29 MLH1 exon 16 deletion (MLH1∆Ex16) carriers, of which five (17%) had not been previously identified in healthcare. Our results demonstrate a high positive predictive value for the identification of MLH1∆Ex16 carriers from genotyping data. The cost-efficient method for detection of CNV carriers from large biobank genotyping cohorts described here facilitates intensified screening and follow-up aiming to cancer prevention.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"47"},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141902","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

Pancreatic adenocarcinoma in a patient with a germline RB1 pathogenic variant. 一种系RB1致病变异患者的胰腺腺癌。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-05-26 DOI: 10.1007/s10689-025-00475-7

Riya Patel, Christos Fountzilas, Michael Horowitz, Emily Schultz, Katherine M Clayback, Erik S Knudsen, Agnieszka K Witkiewicz, Kenan Onel

{"title":"Pancreatic adenocarcinoma in a patient with a germline RB1 pathogenic variant.","authors":"Riya Patel, Christos Fountzilas, Michael Horowitz, Emily Schultz, Katherine M Clayback, Erik S Knudsen, Agnieszka K Witkiewicz, Kenan Onel","doi":"10.1007/s10689-025-00475-7","DOIUrl":"10.1007/s10689-025-00475-7","url":null,"abstract":"Germline pathogenic variants (GPVs) in RB1 are associated with the pediatric-onset intra-ocular malignancy retinoblastoma and typically present in infancy as multi-focal or bilateral disease. Survivors of retinoblastoma are at high risk for developing subsequent malignant neoplasms (SMNs); indeed, these are the leading cause of death for individuals cured of their retinoblastoma. With the exception of sarcomas, typically occurring at the site of antecedent radiation therapy for the original retinoblastoma diagnosis, and melanoma, little is known of other SMNs in retinoblastoma survivors. Here, we describe a unique case of pancreatic adenocarcinoma (PDAC) in a patient with a RB1 GPV who was diagnosed with retinoblastoma as an infant. At age 57, he was diagnosed with PDAC. Sequence analysis of the PDAC revealed the acquisition of a somatic second-hit in RB1 in the PDAC. Multispectral immunofluorescence analyses of the PDAC tumor illustrated selective loss of the RB protein in the tumor that was accompanied by the continued expression of p16ink4a, encoded by the CDKN2A gene. In PDAC, CDKN2A loss is a common early event that contributes to carcinogenesis. This case may suggest that PDAC is a rare late component of RB1-associated tumor predisposition and illustrates that biallelic loss of RB1 is an alternative mechanism by which the RB1-pathway can be disrupted in PDAC independent of CDKN2A inactivation.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"24 2","pages":"46"},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141889","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

Upper GI polyposis and cancer in FAP: diagnosis, surveillance and treatment. FAP中的上消化道息肉病和癌症：诊断、监测和治疗。

IF 1.8 4区医学

Familial Cancer Pub Date : 2025-05-26 DOI: 10.1007/s10689-025-00472-w

Arthur S Aelvoet, Yusaku Shimamoto, Yoji Takeuchi, Evelien Dekker, Carol A Burke, Sonia S Kupfer, Gautam Mankaney

引用次数: 0

Advancing care for Lynch syndrome patients in China: challenges and opportunities. 在中国推进林奇综合征患者的护理：挑战与机遇。

IF 2 4区医学

Familial Cancer Pub Date : 2025-05-12 DOI: 10.1007/s10689-025-00461-z

Shirley V Hodgson, Hans F A Vasen

引用次数: 0