Correction to: Outcomes of retesting in patients with previously uninformative cancer genetics evaluations
(Source: Familial Cancer)
Source: Familial Cancer - October 28, 2021 Category: Cancer & Oncology Source Type: research

Medullary thyroid cancer and pheochromocytoma in MEN2A: are there parent of origin effects on disease expression?
AbstractThere are no data on the impact of parent-of-origin effects on the expression of multiple endocrine neoplasia type 2A (MEN2A). The present study aimed to explore effects of parent-of-origin and offspring gender in MEN2A. In total, 224 carriers harbored heterozygousRET (REarranged duringTransfection) p.Cys634 missense variants, for 169 of whom information on parent-of-origin gender was available. Altogether, offspring from affected fathers harbored more often node metastases from medullary thyroid cancer (45 vs. 19%;P = 0.006) and bilateral pheochromocytoma (24 vs. 10%;P = 0.021) than off...
Source: Familial Cancer - October 22, 2021 Category: Cancer & Oncology Source Type: research

Identification of women at risk of hereditary breast –ovarian cancer among participants in a population-based breast cancer screening
AbstractWomen attending mammography screening may benefit from family history (FH) assessment for the identification of Hereditary Breast Ovarian Cancer (HBOC). Few studies explored the efficacy of tailored educational interventions in driving the attention on FH-associated risk among these women. To compare the efficacy of two educational tools in increasing attention towards FH, 6.802 women with a negative mammography were randomized to receive a note on FH of breast/ovarian cancer (letter A, n  = 3.402) or a note with details on possible implication of FH patterns (letter B, n = 3.200). Upon ...
Source: Familial Cancer - October 20, 2021 Category: Cancer & Oncology Source Type: research

Familial colorectal cancer and tooth agenesis caused by an AXIN2 variant: how do we detect families with rare cancer predisposition syndromes?
We present a three-generation family with anAXIN2 variant and a family history of colorectal cancer (CRC), colon polyps and tooth agenesis. A likely pathogenic variant was detected in theAXIN2 gene (c.1994dup; p.(Asn666Glnfs*41)). This variant has previously been associated with tooth agenesis and polyposis, only. In this case report we describe eight carriers with tooth agenesis and variable clinical findings, including polyps and CRC. Our case provides additional knowledge to the sparse data on genotype –phenotype association related toAXIN2 associated cancer syndrome. Further, our case highlights the importance of...
Source: Familial Cancer - October 12, 2021 Category: Cancer & Oncology Source Type: research

Re-evaluating cancer risks associated with the CHEK2 p.Ser428Phe Ashkenazi Jewish founder pathogenic variant
This study aimed to re-evaluate cancer risks conferred by theCHEK2 S428F variant in Ashkenazi Jews. De-identified data fromCHEK2 S428F variant carriers sequenced with multigene panels were analyzed. Overall, 486/341,531 (0.14%) cases of all ethnicities diagnosed with any cancer type wereCHEK2 S428F carriers, of whom 243/9980 self-identified as Ashkenazi Jews and carried this risk variant only. Compared with ethnically matched non-cancer controls, across all cancer cases, this variant was not more prevalent (p  = 0.271). Specifically, variant prevalence was not different in breast cancer cases compared with co...
Source: Familial Cancer - October 8, 2021 Category: Cancer & Oncology Source Type: research

Positive experiences of healthcare professionals with a mainstreaming approach of germline genetic testing for women with ovarian cancer
AbstractAccording to current guidelines, all women with epithelial ovarian cancer are eligible for genetic testing forBRCA germline pathogenic variants. Unfortunately, not all affected women are tested. We evaluated the acceptability and feasibility for non-genetic healthcare professionals to incorporate germline genetic testing into their daily practice. We developed and implemented a mainstreaming pathway, including a training module, in collaboration with various healthcare professionals and patient organizations. Healthcare professionals from 4 different hospitals were invited to participate. After completing the train...
Source: Familial Cancer - October 7, 2021 Category: Cancer & Oncology Source Type: research

Ovarian carcinoma in children with constitutional mutation of SMARCA4: single-family report and literature review
In this study, we report genetic testing of a family with two children carrying pathogenic germline mutations ofSMARCA4 and summarize the course of SCCOHT in all pediatric patients reported in the literature with constitutional defects identified within theSMARCA4 locus. (Source: Familial Cancer)
Source: Familial Cancer - October 1, 2021 Category: Cancer & Oncology Source Type: research

Outcomes of retesting in patients with previously uninformative cancer genetics evaluations
This study adds to the limited body of literature on ret esting outcomes beyond first-lineBRCA analysis alone and confirms the utility of multigene panel testing. Retesting certain affected individuals when updated GT is available could result in earlier PV/LPV identification, significantly impacting screening recommendations and potentially reducing cancer-related morbidity and mortality. (Source: Familial Cancer)
Source: Familial Cancer - September 21, 2021 Category: Cancer & Oncology Source Type: research

Fibroadenoma in vulval ectopic breast tissue in a patient with PTEN  Hamartoma Tumour Syndrome
AbstractPTEN is a tumour suppressor gene involved in regulating cell division. Pathogenic germline variants inPTEN predispose to benign and malignant growths of numerous organs, including of the breast. In the following report, we describe the first documented case of a fibroadenoma developing in ectopic breast tissue of the vulva in a patient with a germline pathogenic variant inPTEN. This highlights the risk of hyperplasia developing in any breast tissue, including rare ectopic sites, particularly in patients with underlying germline variants in cancer susceptibility genes. (Source: Familial Cancer)
Source: Familial Cancer - September 15, 2021 Category: Cancer & Oncology Source Type: research

Eighth International Symposium on hereditary breast and ovarian cancer
(Source: Familial Cancer)
Source: Familial Cancer - September 15, 2021 Category: Cancer & Oncology Source Type: research

Uterine leiomyomatosis in adolescents and young adults (AYAs) may represent a narrow phenotypic variant of FH tumour predisposition syndrome
AbstractFH Tumour Predisposition Syndrome, also known as Hereditary Leiomyomatosis and renal cell cancer (HLRCC), or Reed Syndrome, is an autosomal dominant condition clinically characterized by multiple cutaneous leiomyomas, multiple early-onset uterine leiomyomas and early-onset renal cell cancer. Here we report a young female with FH Tumour Predisposition Syndrome with no clinical features except early-onset uterine leiomyomas. Whilst there is a significant history of uterine leiomyomas in her family, there is no history of cutaneous leiomyomas or renal cell cancer (RCC). Uterine leiomyomatosis in young ...
Source: Familial Cancer - September 14, 2021 Category: Cancer & Oncology Source Type: research

A de novo pathogenic variant in the MSH6 gene in a 52 years-old woman
AbstractLynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-ol...
Source: Familial Cancer - September 14, 2021 Category: Cancer & Oncology Source Type: research

Unusual phenotypes in patients with a pathogenic germline variant in DICER1
AbstractPathogenic germlineDICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missenseDICER1 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 germlineDICER1 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 p...
Source: Familial Cancer - July 31, 2021 Category: Cancer & Oncology Source Type: research

Patient ethnicity and cascade genetic testing: a descriptive study of a publicly funded hereditary cancer program
AbstractCascade genetic testing for hereditary cancer is highly accurate and cost-effective for identifying individuals at high risk for cancer; however, not all eligible people utilize this service. While sociodemographic factors related to the uptake of cascade genetic testing, such as age and sex, have been fairly well described in the literature, there is limited data available regarding patient ethnicity. We analyzed four years of testing data for this factor, as well as sex, age and genes tested. The patients were seen by the Hereditary Cancer Program of BC Cancer, which serves the entire population of British Columb...
Source: Familial Cancer - July 7, 2021 Category: Cancer & Oncology Source Type: research

Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family
AbstractWhile several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novelNRAS variant (c.170A  >  C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pock...
Source: Familial Cancer - July 3, 2021 Category: Cancer & Oncology Source Type: research

Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group
AbstractDICER1 syndrome is a rare genetic disorder that predisposes to a wide spectrum of tumors. Developing surveillance protocols for this syndrome is challenging because uncertainty exists about the clinical efficacy of surveillance, and appraisal of potential benefits and harms vary. In addition, there is increasing evidence that germlineDICER1 pathogenic variants are associated with lower penetrance for cancer than previously assumed. To address these issues and to harmonize DICER1 syndrome surveillance programs within Europe, the Host Genome Working Group of the European branch of the International Society of Pediatr...
Source: Familial Cancer - June 25, 2021 Category: Cancer & Oncology Source Type: research

PTCH2 is not a strong candidate gene for gorlin syndrome predisposition
AbstractA number of case/family reports have proposedPTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. We assessed our cohort of 21PTCH1/SUFU negative GS families forPTCH2 variants and assessed current evidence from reported cases/families and population data. In ourPTCH1/SUFU variant negative GS cohort (25% of total), no pathogenic or likely pathogenicPTCH2 variants were identified. In addition, none of the previously publishedPTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. The absence of clear pathogenic variants in GS...
Source: Familial Cancer - June 25, 2021 Category: Cancer & Oncology Source Type: research

A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven
This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering w ell without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in theFH gene and its loss of heterozygosity in the tumor...
Source: Familial Cancer - June 22, 2021 Category: Cancer & Oncology Source Type: research

The paradigm of hematological malignant versus non-malignant manifestations, driven by primary immunodeficiencies: a complex interplay
AbstractHematological malignancies (HM) developed on underlying primary immunodeficiencies (PID) are rare and of unusual features. Differentiating between malignant and non-malignant lymphoproliferation in cases of pediatric hematology and oncology and revealing their molecular predisposition demonstrate the complex interplay between PID and HM. We retrospectively studied a case series of seven pediatric patients, all with PID with manifestations raising suspicion for HM or hypereosinophilic syndrome (HES) or confirmed HM of lymphoid origin. Combined immunodeficiency (CID) without detection of a known mutated gene or with ...
Source: Familial Cancer - June 15, 2021 Category: Cancer & Oncology Source Type: research

First international workshop of the ATM and cancer risk group (4-5 December 2019)
This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures forATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes thatATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary. (Source: Familial Cancer)
Source: Familial Cancer - June 14, 2021 Category: Cancer & Oncology Source Type: research

Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome
AbstractComprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germlineTP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36  years [range 3–68], median follow-up 37 months [range 2–70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnos...
Source: Familial Cancer - June 2, 2021 Category: Cancer & Oncology Source Type: research

Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel
In this study we have developed criteria to compile a childhood cance r predisposition gene panel which might ultimately be used in a clinical setting, regardless of the specific type of childhood cancer. This panel will be evaluated in a prospective study. The panel is available on (pediatric-cancer-predisposition-genepanel.nl) and will be regularly updated. (Source: Familial Cancer)
Source: Familial Cancer - June 1, 2021 Category: Cancer & Oncology Source Type: research

Review of guidelines for the identification and clinical care of patients with genetic predisposition for hematological malignancies
AbstractSince WHO has recognized myeloid neoplasms with germline predisposition as a new entity in 2016, it has become increasingly clear that diagnosing familial leukemia has critical implications for both the patient and his/her family, and that interdisciplinary teams of hematologists and clinical geneticists should provide care for this specific patient group. Here, we summarize consensus criteria for the identification and screening of patients with genetic predisposition for hematologic malignancies, as provided by different working groups, e.g. by the Nordic MDS group and the AACR. In addition to typical clinical fe...
Source: Familial Cancer - May 31, 2021 Category: Cancer & Oncology Source Type: research

Questioning the validity of clinically available breast cancer polygenic risk scores: comparison of two labs reveals discrepancies
(Source: Familial Cancer)
Source: Familial Cancer - May 18, 2021 Category: Cancer & Oncology Source Type: research

A recurrent pathogenic BRCA2 exon 5 –11 duplication in the Christian Arab population in Israel
In this study we describe PVs detected in cancer susceptibility genes among a cohort of Christian Arabs from Israel. We reviewed patient records from the Oncogenetic clinic at Rambam Health Care Campus during the years 2013- mid 2020. Thirty-five unrelated Christian Arab patients, with personal or family history of BC and/or OC underwentBRCA1/BRCA2 (14/35) testing or cancer gene panel testing (21/35) as part of their diagnostic workup. Three clinically significant variants inBRCA2, CHEK2 andRAD51C were found in 7/35 patients (20%). A recurrent duplication of theBRCA2 genomic region, encompassing exons 5 –10 and the 5...
Source: Familial Cancer - May 17, 2021 Category: Cancer & Oncology Source Type: research

Pilot study of an online training program to increase genetic literacy and communication skills in oncology healthcare professionals discussing BRCA1/2 genetic testing with breast and ovarian cancer patients
This study assesses the website ’s acceptability and user-friendliness; suggestions for improvement were also elicited. Oncology healthcare professionals were recruited through relevant professional organisations, invited to the study by email, asked to work through the website and then complete an online questionnaire. Thirty-t wo oncology healthcare professionals completed the questionnaire after viewing the website. Nearly all participants were satisfied with the information contained in the program (very satisfied: n = 14/32, 44%, satisfied: n = 17/32, 53%, neither satisfied nor dissat...
Source: Familial Cancer - May 10, 2021 Category: Cancer & Oncology Source Type: research

The psychological impact and experience of breast cancer screening in young women with an increased risk of breast cancer due to neurofibromatosis type 1
AbstractWomen with neurofibromatosis type 1 (NF1) have an increased risk of developing early breast cancer with a poorer prognosis compared to the general population. Therefore, international management guidelines recommend regular screening in women with NF1  starting from 30 to 35 years. As the psychological impacts of breast cancer screening in other high-risk populations cannot be extended to women with NF1, due to increased incidence of cognitive and mental health issues, the psychological harms of breast screening in women with NF1 are unknown. Co nsequently, the aim of this study was to assess the psychological...
Source: Familial Cancer - May 8, 2021 Category: Cancer & Oncology Source Type: research

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management
AbstractPathogenic germline exonuclease domain (ED) variants of  POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with  probably pathogenic variants. We identified patients with a variants mapping to the EDs ofPOLE orPOLD1 from cancer genetics clinics,  a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance...
Source: Familial Cancer - May 5, 2021 Category: Cancer & Oncology Source Type: research

Ovarian carcinoma in children with constitutional mutation of SMARCA4 : single-family report and literature review
In this study, we report genetic testing of a family with two children carrying pathogenic germline mutations ofSMARCA4 and summarize the course of SCCOHT in all pediatric patients reported in the literature with constitutional defects identified within theSMARCA4 locus. (Source: Familial Cancer)
Source: Familial Cancer - April 28, 2021 Category: Cancer & Oncology Source Type: research

In memoriam Professor Thierry Fr ébourg
(Source: Familial Cancer)
Source: Familial Cancer - April 28, 2021 Category: Cancer & Oncology Source Type: research

CDH1 pathogenic variants and cancer risk in an unselected patient population
AbstractCDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact ofCDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identifyCDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant inCDH1. We reviewed electronic health records and BioMe enrollment surveys for pe...
Source: Familial Cancer - April 22, 2021 Category: Cancer & Oncology Source Type: research

Von Hippel-Lindau disease and rapidly progressing pheochromocytomas in siblings
We report a case of two brothers with a strong family history of VHL type 2 due to a pathogenic germline VHL variant, specifically, a surface missense substitution, with a rapidly progressive clinical course that both presented with a large adrenal mass. Both brothers presented with large pheochromocytomas, the earliest presentation being at age 7, despite routine screening. The rapid progression and early presentation of these patients raises an important discussion around the commonly used surveillance protocols for pheochromocytoma in pediatric patients with VHL and missense mutations. We conclude that a more accelerate...
Source: Familial Cancer - April 20, 2021 Category: Cancer & Oncology Source Type: research

Current recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG)
This report summarizes genotype-based recommendations for screening patients withPTCH1 andSUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 inPTCH1, and at age 20 inSUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 forPTCH1 PV carriers only. For medulloblastomas, repeated brain MRI...
Source: Familial Cancer - April 16, 2021 Category: Cancer & Oncology Source Type: research

“I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants
AbstractLittle is known about what uncertainties patients experience after being identified to carry a pathogenic variant in a moderate-risk cancer gene as a result of undergoing multigene panel testing for cancer susceptibility. Data regarding cancer risk estimates and effectiveness of risk management strategies for these variants continues to evolve, which has the potential to evoke uncertainty. Acknowledging uncertainty during pre- and post-test discussions is imperative to helping individuals to adapt to their results. A better understanding of this population ’s experience of uncertainty is needed to facilitate ...
Source: Familial Cancer - April 15, 2021 Category: Cancer & Oncology Source Type: research

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer
AbstractLynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758  bp, mediated byAlu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9 –10 of theMSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10...
Source: Familial Cancer - April 10, 2021 Category: Cancer & Oncology Source Type: research

Malignancy risk in individuals with familial adenomatous polyposis receiving biologics and immunomodulators
AbstractClinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow u...
Source: Familial Cancer - April 6, 2021 Category: Cancer & Oncology Source Type: research

Constitutional 2p16.3 deletion including MSH6 and FBXO11 in a boy with developmental delay and diffuse large B-cell lymphoma
We describe a case of a boy with neurodevelopmental delay and a diffuse large B-cell lymphoma (DLBCL) in whom we discovered a germline de novo 2p16.3 deletion includingMSH6 and part of theFBXO11 gene. A causative role forMSH6 in cancer development was excluded based on tumor characteristics. The constitutionalFBXO11 deletion explains the neurodevelopmental delay in the patient. The FBXO11 protein is involved in BCL-6 ubiquitination and BCL-6 is required for the germinal center reaction resulting in B cell differentiation. Somatic loss of function alterations ofFBXO11 result in BCL-6 overexpression which is a known driver i...
Source: Familial Cancer - April 3, 2021 Category: Cancer & Oncology Source Type: research

Letter to the Editor-Recent advances in Lynch syndrome: response to M øller et al.
(Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research

Letter to the Editor-Recent advances in Lynch syndrome
(Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Letter to the Editor —Recent advances in Lynch syndrome
A correction to this paper has been published: https://doi.org/10.1007/s10689-021-00246-0 (Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research

Extended gene panel testing in lobular breast cancer
AbstractPurpose: Lobular breast cancer (LBC) accounts for  ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC.Methods: 302 women with LBC and 1567 without breast cancer were tested forBRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative forBRCA1/2 PGVs underwent extended screening, including:ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, andTP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were inBRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4),...
Source: Familial Cancer - March 25, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Letter to the Editor —Recent advances in Lynch syndrome: response to Møller et al.
A correction to this paper has been published: https://doi.org/10.1007/s10689-021-00245-1 (Source: Familial Cancer)
Source: Familial Cancer - March 25, 2021 Category: Cancer & Oncology Source Type: research

A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published, unpublished and novel
AbstractBRCA1 andBRCA2 are two prominent genes that account for about 20 –40% of inherited breast cancer. Mutations in these genes are often associated with clustering of especially early-onset cancers in the family. The spectrum ofBRCA variants showed a significant difference between geographic regions and ethnicities. The frequency and spectrum ofBRCA mutations in Iran, a country in southwest Asia, have not yet been thoroughly studied. Here, for the first time, all published and not publishedBRCA pathogenic variants are presented. Among 1040 high risk families (1258 cases) which were detected, 116 families were fou...
Source: Familial Cancer - March 23, 2021 Category: Cancer & Oncology Source Type: research

Adaptation and early implementation of the PREdiction model for gene mutations (PREMM 5 ™) for lynch syndrome risk assessment in a diverse population
We report on preliminary findings based on the first 500 individuals exposed to the adapted application in a primary care population enriched for low-literacy and low-resource patients. Major adaptations to the PREMM5™ provider module included reduction in reading level, addition of interactive literacy aids, incorporation of family history assessment for both maternal and paternal sides of the family, and inclusion of questions about individual relatives or small groups of relatives to reduce cognitive burden . In the first 500 individuals, 90% completed the PREMM5™ independently; of those, 94% did so in 5&nbs...
Source: Familial Cancer - March 23, 2021 Category: Cancer & Oncology Source Type: research

Age of diagnosis in familial Barrett ’s associated neoplasia
AbstractThe identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett ’s esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to no n-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed hi...
Source: Familial Cancer - March 11, 2021 Category: Cancer & Oncology Source Type: research

Knowledge and psychosocial impact of genetic counseling and multigene panel testing among individuals with ovarian cancer
AbstractIn a sample of individuals with ovarian cancer,  we aimed to (a) identify factors associated with the psychosocial impact of genetic counseling and multigene panel testing, (b) identify factors associated with cancer genetics knowledge, and (c) summarize patient-reported recommendations to improve the genetic counseling and multigene panel testi ng process. Eligible participants in this secondary analysis of quantitative and qualitative survey data were English-speaking adults with ovarian cancer. Psychosocial impact was assessed using the Multidimensional Impact of Cancer Risk Assessment (MICRA) question...
Source: Familial Cancer - March 10, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Choose and stay on one out of two paths: distinction between clinical versus research genetic testing to identify cancer predisposition syndromes among patients with cancer
A correction to this paper has been published: https://doi.org/10.1007/s10689-021-00238-0 (Source: Familial Cancer)
Source: Familial Cancer - March 10, 2021 Category: Cancer & Oncology Source Type: research

Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study
AbstractRecognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessme...
Source: Familial Cancer - March 9, 2021 Category: Cancer & Oncology Source Type: research

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronicAPC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detectAPC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germlineAPC variants: c.1408  + 731C >  T, p.(Gly471Serfs*55), c.1408 + 73...
Source: Familial Cancer - March 8, 2021 Category: Cancer & Oncology Source Type: research

Effective identification of cancer predisposition syndromes in children with cancer employing a questionnaire
Conclusion:  The CPS questionnaire appears to significantly improve the diagnosis of children with CPS among children with a newly diagnosed oncologic condition. (Source: Familial Cancer)
Source: Familial Cancer - March 2, 2021 Category: Cancer & Oncology Source Type: research