Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019
(Source: Familial Cancer)
Source: Familial Cancer - July 2, 2020 Category: Cancer & Oncology Source Type: research

Improving primary care identification of familial breast cancer risk using proactive invitation and decision support
This study demonstrated proactive risk assessment in primary care enables accurate identification of women, including many younger women, at increased risk of breast cancer. To improve generalisability across the population, more active me thods of engagement need to be explored.Trial registration: CRUK Clinical Trials  Database 11779. (Source: Familial Cancer)
Source: Familial Cancer - June 11, 2020 Category: Cancer & Oncology Source Type: research

Chemoprevention in familial adenomatous polyposis: past, present and future
AbstractFamilial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research  has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy ...
Source: Familial Cancer - June 8, 2020 Category: Cancer & Oncology Source Type: research

Prospective observational data informs understanding and future management of Lynch syndrome: insights from the Prospective Lynch Syndrome Database (PLSD)
AbstractThe Prospective Lynch Syndrome Database (PLSD) has been developed as an international, multicentre, prospective, observational study that aims to provide age and organ-specific cancer risks according to gene and gender, estimates of survival after cancer and information on the effects of interventions. Recent reports from PLSD provided improved estimates of cancer risks and survival and showed that different time intervals between surveillance colonoscopies did not affect the incidence, stage or prognosis of colorectal cancer. The PLSD reports suggest that current management guidelines for Lynch syndrome should be ...
Source: Familial Cancer - June 8, 2020 Category: Cancer & Oncology Source Type: research

Germline variants discovered in lymphoma patients undergoing tumor profiling: a case series
AbstractClinical tumor sequencing protocols often depend on obtaining germline DNA from patients to aid in the identification of de novo variants in the tumor, and therefore come with the possibility for the incidental discovery of germline variants. Ninety-one adult patients with lymphoma were consented and enrolled in MIONCOSEQ, an IRB-approved tumor profiling protocol that utilizes an exome sequencing platform. Charts were retrospectively reviewed for germline variants from sequencing results, personal and/or family history of cancer and genetic counseling referral. After review of the 91 lymphoma cases, seven (8%) case...
Source: Familial Cancer - June 6, 2020 Category: Cancer & Oncology Source Type: research

Two cases of somatic STK11 mosaicism in Danish patients with Peutz –Jeghers syndrome
We report two Danish patients withSTK11 mosaicism detected in blood when using Next-Generation Sequencing. This is only the sixth and seventh patient reported in the literature, and we compare phenotypes of the reported cases. The results indicate thatSTK11 mosaicism is more frequent than anticipated and highlight that mosaicism should be considered in patients with clinical suspicion of PJS or patients fulfilling the diagnostic criteria. (Source: Familial Cancer)
Source: Familial Cancer - June 6, 2020 Category: Cancer & Oncology Source Type: research

Constitutional mosaicism for a BRCA2 mutation as a cause of early-onset breast cancer
We report on a breast cancer patient with constitutional somatic mosaicism of aBRCA2 mutation.BRCA2 mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). TheBRCA2 mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for aBRCA2 mutation and shows thatBRCA2 mosaicism can underlie early-onset breast cancer....
Source: Familial Cancer - May 28, 2020 Category: Cancer & Oncology Source Type: research

Small fraction of testicular cancer cases may be causatively related to CHEK2 inactivating germ-line mutations: evidence for somatic loss of the remaining CHEK2 allele in the tumor tissue
AbstractA recent study suggested a role ofCHEK2 loss-of-function germ-line pathogenic variants in the predisposition to testicular cancer (TC) (AlDubayan et al. JAMA Oncol 5:514 –522, 2019). We attempted to validate this finding relying on the high population frequency of recurrentCHEK2 pathogenic variants in Slavic populations.CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2  + 1G >  A [c.444 + 1G >  A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR 4.0 (95% CI 1....
Source: Familial Cancer - May 26, 2020 Category: Cancer & Oncology Source Type: research

Low accuracy of self-reported family history of melanoma in high-risk patients
AbstractFamily history of melanoma is a major melanoma risk factor. However, self-reported family histories for some cancers, including melanoma, are commonly inaccurate. We used a unique database, the Utah Population Database (UPDB), as well as the Utah Cancer Registry to determine the accuracy of self-reported family history of melanoma in a large cohort of high-risk patients. Patient charts were reviewed and compared to records in the UPDB and the UCR to confirm personal and family history of melanoma in 1780 patients enrolled in a total body photography monitoring program. Self-reported family history of melanoma in fi...
Source: Familial Cancer - May 21, 2020 Category: Cancer & Oncology Source Type: research

Women ’s responses and understanding of polygenic breast cancer risk information
This study aimed to explore women ’s experience receiving their personalised polygenic risk score (PRS) and compare responses of women at different levels of polygenic risk. Eligible participants were affected and unaffected women from families clinically assessed to be at high risk for breast cancer who had received their persona lised PRS as part of the Variants in Practice Psychosocial Study (ViPPs). In-depth semi-structured interviews were conducted with 21 women (mean age 53.4 years) up to four weeks after receiving their PRS. Interviews were transcribed verbatim and analysed using thematic analysis. Eleven...
Source: Familial Cancer - May 20, 2020 Category: Cancer & Oncology Source Type: research

Biallelic NF1 inactivation in high grade serous ovarian cancers from patients with neurofibromatosis type 1
AbstractNeurofibromatosis type 1 (NF1) is a multisystem disorder caused by germline heterozygousNF1 loss-of-function variants. TheNF1 gene encodes neurofibromin, a RAS GTPase-activating protein, which functions by down-regulating RAS/RAF/MAPK-signalling pathways. SomaticNF1 aberrations frequently occur in sporadic ovarian cancer (OC), but the incidence of OC in NF1 patients is rare. Here we report the germline and somatic findings for two unrelated patients with NF1 and high-grade serous OC. Germline testing revealed a heterozygousNF1 pathogenic variant in each patient, c.7096_7101del (p.Asn2366_Phe2367del) and c.964delA (...
Source: Familial Cancer - May 13, 2020 Category: Cancer & Oncology Source Type: research

Evaluation of implementation of risk management guidelines for carriers of pathogenic variants in mismatch repair genes: a nationwide audit of familial cancer clinics
ConclusionThese results indicate that there is scope to further increase provision of advice at FCCs to ensure that all carriers receive recommendations about evidence-based risk management. A multi-pronged behaviour change and implementation science approach tailored to specific barriers is likely to be needed to achieve optimal clinician behaviours and outcomes for carriers. (Source: Familial Cancer)
Source: Familial Cancer - May 9, 2020 Category: Cancer & Oncology Source Type: research

MLH1 intronic variants mapping to  + 5 position of splice donor sites lead to deleterious effects on RNA splicing
AbstractGermline pathogenic variants in the DNA mismatch repair genes (MMR):MLH1,MSH2,MSH6, andPMS2, are causative of Lynch syndrome (LS). However, many of the variants mapping outside the invariant splice site positions (IVS  ± 1, IVS ± 2) are classified as variants of unknown significance (VUS). Three such variants (MLH1 c.588+5G>C, c.588+5G>T and c.677+5G>A) were identified in 8 unrelated LS families from Argentina, Brazil and Chile. Herein, we collected clinical information on these families and performed segregation analysis and RNA splicing studies to assess the impl...
Source: Familial Cancer - May 4, 2020 Category: Cancer & Oncology Source Type: research

Characterization of a germline splice site variant MLH1 c.678-3T & gt;A in a Lynch syndrome family
In this report, we describe a 42-year-old female with Lynch syndrome who carries a germline variant,MLH1 c.678-3T>A, in the splice acceptor site of intron 8. Functional studies and semiquantitative analysis demonstrated that this variant causes a significant increase in the transcripts with exon 9 or exon 9 and 10 deletions, which presumably leads to premature protein truncation or abnormal protein. In addition, we also observed MSI-H and loss of MLH1 by IHC in patient ’s tumor tissue. This variant also segregated with Lynch Syndrome related cancers in three affected family members. Based on these evidence, theMLH...
Source: Familial Cancer - April 30, 2020 Category: Cancer & Oncology Source Type: research

Cumulative risk of skin cancer in patients with Li-Fraumeni syndrome
AbstractLi-Fraumeni syndrome (LFS) is an inherited cancer syndrome, characterized by an early onset of various types of cancers. LFS is associated with a germline mutation in theTP53 gene. The risk of developing skin cancer in patients with LFS is unknown. To evaluate the cumulative risk of skin cancer in patients with LFS and to compare this risk to the general Dutch population. In this retrospective cohort study, all provenTP53 mutation carriers in the Netherlands Cancer Institute were included from their first visit to the Institute until June 2017. Medical charts and pathology reviews cross-referenced with PALGA, the n...
Source: Familial Cancer - April 30, 2020 Category: Cancer & Oncology Source Type: research

Primary fallopian tube carcinoma (PFTC) in a BRIP-1 mutation carrier: the first case report
AbstractSome hereditary ovarian cancer cases can be associated with a mutation of a gene involved in the DNA double-strand break repair system other than BRCA, such as BRIP1. This mutation is an emerging indication for prophylactic risk-reducing salpingo-oophorectomy (RRSO): however, anomalous tubal pathologic lesions have not yet been reported during RRSO performed for this specific indication (BRIP1), as largely reported for BRCA mutation carriers. An asymptomatic 64-year-old woman with a family history of ovarian and breast cancer agreed to undergo RRSO for a pathogenic variant of the BRIP1 gene (heterozygous NM_03204...
Source: Familial Cancer - April 24, 2020 Category: Cancer & Oncology Source Type: research

Systematic development of a training program for healthcare professionals to improve communication about breast cancer genetic counseling with low health literate patients
AbstractThere is a disproportionate underuse of genetic testing in breast cancer patients from lower education or migrant background. Within these groups, communication about referral to genetic counseling appears challenging due to limited health literacy and cultural barriers. Our aim was to develop and evaluate a training program for healthcare professionals (breast surgeons and specialized nurses), to increase effective communication. We systematically developed a blended training program based on patients ’ and healthcare professionals’ needs and preferences. Prior to the training, we assessed awareness, k...
Source: Familial Cancer - April 22, 2020 Category: Cancer & Oncology Source Type: research

Highly aggressive thoracic desmoid tumors in adolescent siblings with fatal outcomes in an FAP kindred: a need for increased vigilance and intervention in at-risk AYAs
AbstractDesmoid tumors are a manifestation of familial adenomatous polyposis (FAP), associated with mutation of theAPC gene. Although considered benign tumors, desmoids can be aggressive and cause considerable morbidity. Known risk factors for desmoid tumor growth include location of mutations within theAPC gene, family history of desmoid tumors, previous surgery, female gender, and pregnancy. Desmoids occur at diverse sites, commonly within the abdomen or at sites of previous surgery; thoracic desmoids are relatively uncommon. Reported here is a highly desmoid tumor-prone FAP family with a truncating mutation in theAPC ge...
Source: Familial Cancer - April 13, 2020 Category: Cancer & Oncology Source Type: research

Waiting and “weighted down”: the challenge of anticipatory loss for individuals and families with Li-Fraumeni Syndrome
In this study, losses were compounded by profound uncertainty, a chronic feature of LFS, which compromised mourning. Long-term engagement of menta l health providers with bereavement training, in partnership with genetics providers, can provide invaluable educational and psychological support to families as they navigate these implacable challenges. (Source: Familial Cancer)
Source: Familial Cancer - March 28, 2020 Category: Cancer & Oncology Source Type: research

Genetic health professionals ’ experiences with initiating reanalysis of genomic sequence data
AbstractDespite the increased diagnostic yield associated with genomic sequencing (GS), a sizable proportion of patients do not receive a genetic diagnosis at the time of the initial GS analysis. Systematic data reanalysis leads to considerable increases in genetic diagnosis rates yet is time intensive and leads to questions of feasibility. Few policies address whether laboratories have a duty to reanalyse and it is unclear how this impacts clinical practice. To address this, we interviewed 31 genetic health professionals (GHPs) across Europe, Australia and Canada about their experiences with data reanalysis and variant re...
Source: Familial Cancer - March 21, 2020 Category: Cancer & Oncology Source Type: research

Analysis of 3297 individuals suggests that the pathogenic germline 5 ′-UTR variant BRCA1 c.-107A  & gt;  T is not common in south-east Germany
In this study we aim to determine the prevalence of the recently identified pathogenicBRCA1 variant c.-107A  >  T in the south-east German population. This variant causes the epigenetic silencing of theBRCA1 promotor and has been detected in two independent families from the UK without a germlineBRCA1 orBRCA2 pathogenic variant. A total of 3297 individuals with suspicion of hereditary breast and ovarian cancer and fulfilling the clinical criteria necessary for genetic testing in Germany were analyzed for presence of the variant by a Kompetitive Allele-Specific PCR (KASP) assay or direct Sanger sequencing. ...
Source: Familial Cancer - March 21, 2020 Category: Cancer & Oncology Source Type: research

De novo SDHB gene mutation in a family with extra-adrenal paraganglioma
We present the second case of a family with ade novo SDHB mutation. (Source: Familial Cancer)
Source: Familial Cancer - March 21, 2020 Category: Cancer & Oncology Source Type: research

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance
In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substa ntial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance. (Source: Familial Cancer)
Source: Familial Cancer - March 19, 2020 Category: Cancer & Oncology Source Type: research

Lack of evidence for CDK12 as an ovarian cancer predisposing gene
AbstractCDK12 variants were investigated as a genetic susceptibility to ovarian cancer in a series of 416 unrelated and consecutive patients with ovarian carcinoma and who carry neither germlineBRCA1 norBRCA2 pathogenic variant. The presence ofCDK12 variants was searched in germline DNA by massive parallel sequencing on pooled DNAs. The lack of detection of deleterious variants and the observed proportion of missense variants in the series of ovarian carcinoma patients as compared with all human populations strongly suggests thatCDK12 is not an ovarian cancer predisposing gene. (Source: Familial Cancer)
Source: Familial Cancer - March 14, 2020 Category: Cancer & Oncology Source Type: research

Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis
AbstractMultigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statem...
Source: Familial Cancer - March 14, 2020 Category: Cancer & Oncology Source Type: research

Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - February 27, 2020 Category: Cancer & Oncology Source Type: research

Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention
In conclusion, mostBRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy inBRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven. (Source: Familial Cancer)
Source: Familial Cancer - February 24, 2020 Category: Cancer & Oncology Source Type: research

Increased prevalence of Barrett ’s esophagus in patients with MUTYH -associated polyposis (MAP)
AbstractBarrett ’s oesophagus (BE) has been associated with an increased risk of both colorectal adenomas and colorectal cancer. A recent investigation reported a high frequency of BE in patients with adenomatous polyposis coli (APC)-associated polyposis (FAP). The aim of the present study is to evaluate the prevalence of BE in a large cohort of patients withMUTYH-associated polyposis (MAP) andAPC-associated adenomatous polyposis. Patients with a genetically confirmed diagnosis of familial adenomatous polyposis (FAP) or MAP were selected and upper gastrointestinal (GI) endoscopy reports, pathology reports of upper GI...
Source: Familial Cancer - February 22, 2020 Category: Cancer & Oncology Source Type: research

Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer
AbstractThe advent of gene panel testing is challenging the previous practice of using clinically defined cancer family  syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have a pplied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 andPMS2) to an Australian population-based case –control-family study of breast cancer. Altogether, eig...
Source: Familial Cancer - February 14, 2020 Category: Cancer & Oncology Source Type: research

Novel intronic variant in PALB2 gene and effective prevention of Fanconi anemia in family
AbstractDespite the acceptance of NextGen sequencing as a diagnostic modality suitable for probands and carriers of Mendelian diseases, its efficiency in identifying causal mutations is limited by both technical aspects of variant call algorithms and by imperfect, consensus-based criteria for assessing the pathogenicity of the findings. Here we describe the medical history of the family with a child born with Fanconi anemia. In this case, typical diagnostic routines were complicated by unusual combination of mutations.PALB2 variant NM_024675.3:c.172_175delTTGT (p.Gln60Argfs) in maternal sample, previously classified as a d...
Source: Familial Cancer - February 12, 2020 Category: Cancer & Oncology Source Type: research

Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report
AbstractMultiple Endocrine Neoplasia (MEN) type 4 is a rare genetic condition that results from variants of theCDKN1B gene and predisposes individuals to develop endocrine tumors. Spinal neurofibromatosis (SNF) is an uncommon subtype of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas of all spinal roots. Here we report a case of the co-occurrence of these syndromes, which has not yet been described in the literature. A male in his 60s presented with Gleason 5  + 4 localized prostate adenocarcinoma treated with radical prostatectomy. Two years later, he developed liver and bone metastas...
Source: Familial Cancer - February 12, 2020 Category: Cancer & Oncology Source Type: research

Missense PALB2 germline variant disrupts nuclear localization of PALB2 in a patient with breast cancer
In conclusion, our studies provided the functional evidence showing the deleterious effect of c.3251C>T, and non-deleterious effects of c.1054G>C and c.1057A>G. Using the ClinGen Pathogenicity calculator, c.3251C>T remains a VUS while c.1054G>C and c.1057A>G may be classified as likely benign variants. (Source: Familial Cancer)
Source: Familial Cancer - February 11, 2020 Category: Cancer & Oncology Source Type: research

Abstracts of the 4th meeting of the European Hereditary Tumour Group, Barcelona, Spain, October 17 –19th, 2019
(Source: Familial Cancer)
Source: Familial Cancer - February 7, 2020 Category: Cancer & Oncology Source Type: research

Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics
AbstractRoutine diagnostics for colorectal cancer patients suspected of having Lynch-Syndrome (LS) currently uses Next-Generation-Sequencing (NGS) of targeted regions within the DNA mismatch repair (MMR) genes. This analysis can reliably detect nucleotide alterations and copy-number variations (CNVs); however, CNV-neutral rearrangements comprising gene inversions or large intronic insertions remain undetected because their breakpoints are usually not covered. As several founder mutations exist for LS, we established PCR-based screening methods for five known rearrangements inMLH1,MSH2, orPMS2, and investigated their preval...
Source: Familial Cancer - January 30, 2020 Category: Cancer & Oncology Source Type: research

Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway
AbstractStudies have shown that a significant number of eligible breast cancer patients are not offered genetic testing or referral to genetic counseling. To increase access to genetic testing in South Eastern Norway, testing has since 2014 been offered directly to breast cancer patients by surgeons and oncologists. This practice is termed “mainstreamed genetic testing”. The aim of this study was to investigate to what extent patients in South Eastern Norway are offered testing. Three hundred and sixty one patients diagnosed in 2016 and 2017 at one regional and one university hospital in South Eastern Norway we...
Source: Familial Cancer - January 30, 2020 Category: Cancer & Oncology Source Type: research

Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients
AbstractThe hallmark of Lynch syndrome (LS)-associated neoplasia is DNA mismatch repair protein (MMR) deficiency. Recent studies have demonstrated that histologically normal colonic crypts in patients with LS can exhibit deficient MMR expression. The aim of this study was to determine the feasibility of detecting MMR deficient crypts in random colonoscopic biopsies of normal mucosa in patients with and without LS. Forty-nine patients, including 33 with LS, 12 without LS, and 4 with germline MMR gene variants of uncertain significance (VUS), were prospectively and blindly evaluated by immunohistochemistry for MMR deficient ...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study
AbstractTo prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers ’ attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent ...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research

Neurofibromatosis type 2 discordance in monozygous twins
AbstractNeurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in theNF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence ofNF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of theNF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System ...
Source: Familial Cancer - January 21, 2020 Category: Cancer & Oncology Source Type: research

De novo pathogenic germline variant in PALB2 in a patient with pancreatic cancer
AbstractDe novo mutations in the major breast/ovarian cancer susceptibility genesBRCA1 andBRCA2 are rare.De novo mutations in thePALB2 gene have never been reported. Here we report ade novo PALB2 germ line mutation (c.3455delC (p.Pro1152Hisfs*11) in a patient with pancreatic cancer, where non-paternity and somatic parental mosaicism have to the extent possible been excluded as a mechanism for detecting thede novo mutation. The lack of previous reports onde novo PALB2 mutations maybe the limited number ofPALB2germline mutations reported overall. (Source: Familial Cancer)
Source: Familial Cancer - December 19, 2019 Category: Cancer & Oncology Source Type: research

The (ir)relevance of the abandoned criterion II for the diagnosis of serrated polyposis syndrome: a retrospective cohort study
AbstractThe World Health Organization (WHO) recently updated the diagnostic criteria for serrated polyposis syndrome (SPS). One of the three previous diagnostic criteria (criterion II2010) is now abandoned:  ≥ 1 serrated polyp (SP) proximal to the sigmoid in a first-degree relative (FDR) of a patient with SPS. Individuals fulfilling this abandoned criterion now receive the same surveillance recommendations as all FDRs of patients with SPS. We aimed to compare the incidence of advanced neoplasia (AN) in FDRs with vs. without fulfillment of the abandoned criterion II2010. We retrospectively recruited FDRs of...
Source: Familial Cancer - December 18, 2019 Category: Cancer & Oncology Source Type: research

Renal cell carcinoma in young FH mutation carriers: case series and review of the literature
AbstractHereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18  years, and a third patient with a...
Source: Familial Cancer - December 2, 2019 Category: Cancer & Oncology Source Type: research

‘We don’t know for sure’: discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations
AbstractPre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors ’ communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations o...
Source: Familial Cancer - November 26, 2019 Category: Cancer & Oncology Source Type: research

Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li –Fraumeni syndrome)
AbstractThe risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li –Fraumeni syndrome (LFS) or Li–Fraumeni Like (LFL) patients. However, the type ofTP53 pathogenic germline variant may possibly influence this risk.TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenicTP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germlineTP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were follo...
Source: Familial Cancer - November 20, 2019 Category: Cancer & Oncology Source Type: research

MLH1 promoter hypermethylation: are you absolutely sure about the absence of MLH1 germline mutation? About a new case
AbstractLynch syndrome accounts for 3 –5% of colorectal cancers and is due to a germline mutation in one of the mismatch repair genesMLH1,MSH2,MSH6, andPMS2. Somatic hypermethylation of theMLH1 promoter is commonly associated to sporadic cases. Strategies have been developed to identify patients with Lynch Syndrome based on clinical findings, tumoral phenotype, family history and immunohistochemistry analysis. However, there still are some pitfalls in this strategy, possibly responsible for an underdiagnosis of Lynch syndrome. Here we report the case of a 37 years-old man presenting with two concomitant tumors locate...
Source: Familial Cancer - November 19, 2019 Category: Cancer & Oncology Source Type: research

Clear cell chondrosarcoma in Von Hippel-Lindau disease
In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of theVHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL. (Source: Familial Cancer)
Source: Familial Cancer - October 31, 2019 Category: Cancer & Oncology Source Type: research

Long-term positive psychological outcomes in an Australian pancreatic cancer screening program
AbstractScreening for pancreatic cancer (PC) in high-risk groups aimed to detect early cancers is currently done only in the research setting, and data on psychological outcomes of screening in these populations is scarce. To determine the psychological impact of a national Australian pancreatic screening program, a prospective study was conducted using validated psychological measures: impact of events scale (IES), psychological consequences questionnaire (PCQ) and the cancer worry scale. Measures were administered at baseline, 1-month and at 1-year post-enrolment and correlations with abnormal endoscopic ultrasound (EUS)...
Source: Familial Cancer - October 17, 2019 Category: Cancer & Oncology Source Type: research

A unique case of two somatic APC mutations in an early onset cribriform-morular variant of papillary thyroid carcinoma and overview of the literature
This report presents a rare sporadic case of CMV-PTC, and to the best of our knowledge the first featuring two somaticAPC mutations underlying the disease, with an overview of CMV-PTC cases with detectedAPC andCTNNB1 pathogenic variants from the literature. (Source: Familial Cancer)
Source: Familial Cancer - October 9, 2019 Category: Cancer & Oncology Source Type: research

Novel candidates in early-onset familial colorectal cancer
This study provides potential novel candidate variants in unexplained familial CRC patients, however, functional validation is imperative to confirm the role of these variants in CRC tumorigenesis. Additionally, while whole exome sequencing enables detection of variants throughout the exome, other causes explaining the familial phenotype such as multiple single nucleotide polymorphisms accumulating to a polygenic risk or epigenetic events, might be missed with this approach. (Source: Familial Cancer)
Source: Familial Cancer - September 25, 2019 Category: Cancer & Oncology Source Type: research

Inequities in multi-gene hereditary cancer testing: lower diagnostic yield and higher VUS rate in individuals who identify as Hispanic, African or Asian and Pacific Islander as compared to European
AbstractThe identification of germline pathogenic/likely pathogenic (P/LP) variants in cancer predisposition genes can guide treatment and management decisions for the individual being tested and potentially at-risk relatives. Prior studies have raised concerns of racial/ethnic disparities in the detection rates of P/LP variants and variants of uncertain significance (VUSs). In 2018, Color Genomics ™, a commercial laboratory, made de-identified, aggregate genetic and clinical information from 50,000 individuals who completed testing for 30 cancer predisposition genes publicly available. It is the largest publicly ava...
Source: Familial Cancer - September 17, 2019 Category: Cancer & Oncology Source Type: research

Health behaviours and beliefs in individuals with familial pancreatic cancer
AbstractIndividuals at high risk for pancreatic cancer are recommended surveillance and healthy lifestyle behaviours and patient experience with recommendations are understudied. To describe engagement and experience with surveillance, tobacco and alcohol use, health beliefs and motivation (Champion Health Belief Measure) and the relationship with personal, psychosocial (Impact of Event Scale), and familial characteristics. Interest in integrative therapies (complementary therapies) are described. A multi-site cross-sectional survey including individuals at high risk for pancreatic cancer with no diagnosis of pancreatic ca...
Source: Familial Cancer - September 14, 2019 Category: Cancer & Oncology Source Type: research