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

Proportion of children with cancer that have an indication for genetic counseling and testing based on the cancer type irrespective of other features
Abstract In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique mutation/methylation signatures may indicate the presence of an underlying cancer predisposition syndrome (CPS). The proportion of children with a cancer type suggesting a CPS among all children with cancer is unknown. To determine the proportion of children with cancer types suggesting an underlying CPS among children with cancer. We evaluated the number of children with cancer types strongly associated with CPS diagnosed in Germany between 2007 and 2016....
Source: Familial Cancer - February 26, 2021 Category: Cancer & Oncology Source Type: research

Managing gastric cancer risk in lynch syndrome: controversies and recommendations
(Source: Familial Cancer)
Source: Familial Cancer - February 21, 2021 Category: Cancer & Oncology Source Type: research

The needs of Southeast Asian BRCA mutation carriers considering risk-reducing salpingo-oophorectomy: a qualitative study
This study aimed to explore the decision-making needs of Malaysian BRCA mutation carriers as an exemplar for the Southeast Asian community. In-depth interviews and clinic observations were conducted with 31 BRCA mutation carriers and analysed thematically. The core theme identified was ‘Coping with complex information and alleviating uncertainties’ with the following subthemes: (1) the need for an adjustment period, (2) information support, (3) social support and, (4) religious support. We found that women required time to accept their BRCA mutation status before they were rea dy to make a risk-reducing choice;...
Source: Familial Cancer - February 19, 2021 Category: Cancer & Oncology Source Type: research

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
(Source: Familial Cancer)
Source: Familial Cancer - February 12, 2021 Category: Cancer & Oncology Source Type: research

Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK
ConclusionsCTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF.CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. NegativeCTNNB1 results, alongside clinical assessment, should promptAPC testing and/or colonoscopy. (Source: Familial Cancer)
Source: Familial Cancer - February 6, 2021 Category: Cancer & Oncology Source Type: research

Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group
AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e.SMARCB1 (RTPS1) andSMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs inSMARCB1 andSMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterize...
Source: Familial Cancer - February 3, 2021 Category: Cancer & Oncology Source Type: research

Genetic predisposition to prostate cancer: an update
AbstractImprovements in DNA sequencing technology and discoveries made by large scale genome-wide association studies have led to enormous insight into the role of genetic variation in prostate cancer risk. High-risk prostate cancer risk predisposition genes exist in addition to common germline variants conferring low-moderate risk, which together account for over a third of familial prostate cancer risk. Identifying men with additional risk factors such as genetic variants or a positive family history is of clinical importance, as men with such risk factors have a higher incidence of prostate cancer with some evidence to ...
Source: Familial Cancer - January 24, 2021 Category: Cancer & Oncology Source Type: research

Interpretation of BRCA2 Splicing Variants: A Case Series of Challenging Variant Interpretations and the Importance of Functional RNA Analysis
We present fourBRCA2 splice site variants with complex variant interpretations (BRCA2 c.68-3T>G, c.68-2A>G, c.425G>T, c.8331+2T>C). Evidence supporting a pathogenic classification is available for each variant, including in silico models, absence in population databases, and published functional data. However, comprehensive RNA analysis showed that some functional transcript may be produced by each variant.BRCA2 c.68-3T>G results in a partial splice defect. ForBRCA2 c.68-2A>G and c.425G>T, aberrant splicing was shown to produce a potentially functional, in-frame transcript.BRCA2 c.8331+2T>C may util...
Source: Familial Cancer - January 20, 2021 Category: Cancer & Oncology Source Type: research

Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome
In this report, we will discuss the implications of these new findings for the development of new surveillance protocols. (Source: Familial Cancer)
Source: Familial Cancer - January 19, 2021 Category: Cancer & Oncology Source Type: research

Comparison of universal screening in major lynch-associated tumors: a systematic review of literature
AbstractLynch syndrome (LS) is associated with an increased lifetime risk of several cancers including colorectal (CRC), endometrial (EC), ovarian (OC), urinary (UT) and sebaceous tumors (ST). The benefit for universal screening in CRC and EC is well known. However, this benefit in other major lynch-associated tumors is unclear. We performed a systematic review of all published articles in the MEDLINE database between 2005 to 2017 to identify studies performing universal screening for LS in unselected CRC, EC, OC, UT and ST. All cases with MSI-H (instability in two or more markers) or missing one or more proteins on IHC te...
Source: Familial Cancer - January 11, 2021 Category: Cancer & Oncology Source Type: research

The CAPP II trial of aspirin in Lynch syndrome/HNPCC: is it time for everyone to be treated?
(Source: Familial Cancer)
Source: Familial Cancer - January 9, 2021 Category: Cancer & Oncology Source Type: research

Genetic evaluation of patients and families with concern for hereditary endocrine tumor syndromes
AbstractHereditary endocrine tumor syndromes are rare conditions with overlapping features. It is imperative that healthcare providers differentiate between these syndromes for proper patient care. Advances in genetic testing technologies have increased utilization of genetic counseling and testing in this field; however, few endocrine cancer genetics clinics exist. Two years ago, a genetic counselor (GC) specializing in endocrine cancer genetics was added to the multidisciplinary team of the James Neuroendocrine/Thyroid Clinic at The Ohio State University. Here, we report on this experience. In total, 358 patients were se...
Source: Familial Cancer - January 7, 2021 Category: Cancer & Oncology Source Type: research

Atypical choroidal nevus in a subject with a germline PALB2 pathogenic variant
AbstractRecent evidence suggests thatPALB2 variants may increase risk for the development of uveal melanoma and uveal melanocytic neoplasms. Here we report a case of an atypical choroidal nevus in a patient with a personal history of cancer and pathogenicPALB2 germline variant. A 75-year-old white female presented with an elevated predominantly amelanotic choroidal lesion OS. On examination and ophthalmic imaging, the mass measured 8.8  mm × 6.5 mm × 1.5 mm. The mass showed predominantly medium to high reflectivity on diagnostic A-scan and acoustic hollowing on B-scan....
Source: Familial Cancer - January 6, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Infantile fibrosarcoma with TPN3-NTRK3 fusion in a boy with Bloom Syndrome
In the original article it was not clear that the senior authorship of this report is shared by D Schindler and S Meyer, reflecting the contributions made. The senior authorship should now be recognised as being shared. (Source: Familial Cancer)
Source: Familial Cancer - January 6, 2021 Category: Cancer & Oncology Source Type: research

Hereditary medullary thyroid carcinoma syndromes: experience from western India
AbstractThe data from the Indian subcontinent on Medullary thyroid carcinoma (MTC) and associated endocrinopathies in hereditary MTC (HMTC) syndromes are limited. Hence, we analyzed clinical and biochemical characteristics, management, and outcomes of HMTC and other associated endocrinopathies [Pheochromocytoma (PCC) and Primary hyperparathyroidism (PHPT)] and compared with apparently sporadic MTC. The records of 97 (51 sporadic and 46 hereditary) consecutive MTC patients were retrospectively analyzed.RET mutation was available in 38 HMTC patients. HMTC group was subclassified into Multiple endocrine neoplasia (MEN) 2A ind...
Source: Familial Cancer - January 4, 2021 Category: Cancer & Oncology Source Type: research

Infantile fibrosarcoma with TPM3-NTRK1 fusion in a boy with Bloom syndrome
We report the clinical and genetic details of a boy who first presented with infantile fibrosarcoma (IFS) at the age of 6  months and subsequently was diagnosed with BS at the age of 9 years. Molecular analysis identified the pathogenic germlineBLM sequence variants (c.1642C>T and c.2207_2212delinsTAGATTC). This is the first report of IFS related to BS, for which we show that bothBLM alleles are maintained in the tumor and demonstrate a TPM3-NTKR1 fusion transcript in the IFS. Our communication emphasizes the importance of long-term follow up after treatment for pediatric neoplastic conditions, as clues to imp...
Source: Familial Cancer - November 21, 2020 Category: Cancer & Oncology Source Type: research

Efficacy of paired tumor and germline testing in evaluation of patients with Lynch-like syndrome in a large integrated healthcare setting
AbstractPatients with mismatch repair (MMR) deficient colorectal cancer (CRC) without detectable germline pathogenic variants (PVs) or likely pathogenic variants (LPVs) in MMR genes are often labeled as Lynch-like syndrome (LLS). We sought to evaluate the efficacy of paired tumor and germline testing in risk stratification of patients with LLS in a large, community-based, integrated healthcare setting. Through the universal screening program for Lynch syndrome at Kaiser Permanente Northern California, we identified all patients with MMR deficient colorectal tumors without detectable germline PVs or LPVs between April 2011 ...
Source: Familial Cancer - November 20, 2020 Category: Cancer & Oncology Source Type: research

Early-onset malignant phyllodes breast tumor in a patient with germline pathogenic variants in NF1 and BRCA1 genes
In conclusion, we present the first case of a malignant phyllodes tumor of the breast in patient carrying pathogenic variants inNF1 andBRCA1. Further studies will be necessary to understand if the phyllodes histotype represents a very rare component of NF1-associated breast cancer. (Source: Familial Cancer)
Source: Familial Cancer - November 19, 2020 Category: Cancer & Oncology Source Type: research