Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes
AbstractKabuki syndrome is a well-recognized syndrome characterized by facial dysmorphism and developmental delay/intellectual disability and in the majority of patients a germline variant inKMT2D is found. As somaticKMT2D variants can be found in 5 –10% of tumors a tumor predisposition in Kabuki syndrome is discussed. So far less than 20 patients with Kabuki syndrome and a concomitant malignancy have been published. Here we report on a female patient with Kabuki syndrome and a c.2558_2559delCT germline variant inKMT2D who developed an embryonal rhabdomyosarcoma (ERMS) at 10 years. On tumor tissue we performed DNA-meth...
Source: Familial Cancer - July 19, 2022 Category: Cancer & Oncology Source Type: research
Prevalence of FANCM germline variants in BRCA1/2 negative breast and/or ovarian cancer patients from Pakistan
AbstractThe Fanconi anemia complementation group M (FANCM) gene is a potential candidate for breast/ovarian cancer susceptibility in European populations. Here, we examined the contribution ofFANCM germline variants to hereditary breast and/or ovarian cancer in Pakistan. ComprehensiveFANCM variant screening was performed in 201BRCA1 andBRCA2 (BRCA1/2) negative Pakistani patients with and without triple-negative breast cancer (TNBC) and/or ovarian cancer, using denaturing high-performance liquid chromatography analysis (DHPLC) followed by DNA sequencing. Novel variants were tested for their potential effect on protein funct...
Source: Familial Cancer - July 8, 2022 Category: Cancer & Oncology Source Type: research
A case of Rothmund-Thomson syndrome originally thought to be a case of Bloom syndrome
AbstractRothmund-Thomson syndrome, a heterogeneous genodermatosis with autosomal recessive hereditary pattern, is an uncommon cancer susceptibility genetic syndrome. To date, only 400 cases have been reported in the literature, and the severity of the features varies among individuals with the condition. Here, we describe a 55-year-old male who had been diagnosed with Bloom Syndrome during childhood due to the suggestive physical features such as short stature, chronic facial erythema, poikiloderma in face and extremities, microtia and microcephaly. However, the genetic test demonstrated that the patient carried two pathog...
Source: Familial Cancer - July 4, 2022 Category: Cancer & Oncology Source Type: research
Universal tumor screening for lynch syndrome on colorectal cancer biopsies impacts surgical treatment decisions
AbstractUniversal tumor screening (UTS) for Lynch syndrome (LS) on colorectal cancer (CRC) can be performed on biopsies or resection specimens. The advantage of biopsies is the chance to provide preoperative genetic counseling/testing (GC/T) so patients diagnosed with LS can make informed decisions regarding resection extent. We evaluated utilization of UTS on biopsies, percentage of patients with deficient mismatch repair (dMMR) who underwent GC/T preoperatively, and whether surgical/treatment decisions were impacted. We performed a retrospective review of medical records to assess CRC cases with dMMR immunohistochemica...
Source: Familial Cancer - June 23, 2022 Category: Cancer & Oncology Source Type: research
Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients
AbstractThe aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radia...
Source: Familial Cancer - June 20, 2022 Category: Cancer & Oncology Source Type: research
Mainstreaming germline genetic testing for patients with pancreatic cancer increases uptake
Conclusions Mainstreaming genetic testing expands access for PC patients without overwhelming genetic counseling resources. (Source: Familial Cancer)
Source: Familial Cancer - June 17, 2022 Category: Cancer & Oncology Source Type: research
A large family with MSH3-related polyposis
We describe the phenotype of a third family, the largest thus far, with adenomatous polyposis related to compound heterozygousMSH3 pathogenic variants. The index patient was a 55-years old male diagnosed with rectal cancer and adenomatous polyposis (cumulatively 52 polyps), with a family history of colorectal polyposis with unknown cause. Next-generation sequencing and copy number variation analysis of a panel of genes associated with colorectal cancer and polyposis revealed compound heterozygous germline pathogenic variants in theMSH3 gene. Nine out of 11 siblings were genotyped. Three siblings carried the same compound h...
Source: Familial Cancer - June 8, 2022 Category: Cancer & Oncology Source Type: research
Prevalence and risk factors of barrett ’s esophagus in lynch syndrome
AbstractLynch syndrome (LS), the most common hereditary cause of colorectal cancer, predisposes to upper gastrointestinal neoplasia. The prevalence of Barrett ’s esophagus (BE) is elevated in some hereditary gastrointestinal cancer syndromes but has not been systematically evaluated in LS. We assessed the prevalence of BE, BE-related dysplasia, esophageal adenocarcinoma (EAC), and factors associated with BE in LS. Asymptomatic patients with a germline p athogenic variant (PV) in the DNA mismatch repair (MMR) genes undergoing EGD for LS surveillance were identified from a hereditary colorectal cancer registry. We assessed...
Source: Familial Cancer - June 2, 2022 Category: Cancer & Oncology Source Type: research
Founder vs. non-founder BRCA1/2 pathogenic alleles: the analysis of Belarusian breast and ovarian cancer patients and review of other studies on ethnically homogenous populations
AbstractThe spectrum ofBRCA1/2 mutations demonstrates significant interethnic variations. We analyzed for the first time the entireBRCA1/2 coding region in 340 Belarusian cancer patients with clinical signs ofBRCA1/2-related disease, including 168 women with bilateral and/or early-onset breast cancer (BC), 104 patients with ovarian cancer and 68 subjects with multiple primary malignancies involving BC and/or OC.BRCA1/2 pathogenic alleles were detected in 98 (29%) women, with 67 (68%) of these being represented by founder alleles. Systematic comparison with other relevant studies revealed that the founder effect observed in...
Source: Familial Cancer - May 21, 2022 Category: Cancer & Oncology Source Type: research
Truncating TINF2 p.Tyr312Ter variant and inherited breast cancer susceptibility
AbstractTINF2 is a critical subunit of the shelterin complex, which protects and maintains the length of telomeres. Pathogenic missense and truncatingTINF2 mutations are causative for dyskeratosis congenita (DC), a rare, dominantly inherited bone marrow failure syndrome characterized by mucocutaneous abnormalities and cancer predisposition. Recent reports indicate that specificTINF2 truncating mutations act as high penetrance cancer predisposition alleles outside DC context, including breast cancer in their tumor spectrum. Here, we have evaluated the role of germline mutations inTINF2 and other shelterin genes in inherited...
Source: Familial Cancer - May 20, 2022 Category: Cancer & Oncology Source Type: research
Long-term chemoprevention in patients with adenomatous polyposis coli: an observational study
This study prov ides evidence that chemoprevention with sulindac is effective and safe and can, either alone or in combination with other drugs, become a long-term management option in cases of adenomatous polyposis. These results justify further long-term prospective chemoprevention studies to elaborate treatment protocols and guidelines. (Source: Familial Cancer)
Source: Familial Cancer - May 16, 2022 Category: Cancer & Oncology Source Type: research
Healthcare professionals ’ perspectives on implementation of universal tumor DNA testing in ovarian cancer patients: multidisciplinary focus groups
AbstractUniversal tumor DNA testing in epithelial ovarian cancer patients can function not only as an efficient prescreen for hereditary cancer testing, but may also guide treatment choices. This innovation, introduced as Tumor-First workflow, offers great opportunities, but ensuring optimal multidisciplinary collaboration is a challenge. We investigated factors that were relevant and important for large-scale implementation. In three multidisciplinary online focus groups, healthcare professionals (gynecologic oncologists, pathologists, clinical geneticists, and clinical laboratory specialists) were interviewed on factors ...
Source: Familial Cancer - May 16, 2022 Category: Cancer & Oncology Source Type: research
Preimplantation genetic testing in patients with genetic susceptibility to cancer
AbstractData on preimplantation genetic testing (PGT-M) in patients with genetic susceptibility to cancer are scarce in the literature, while there is, in our experience, a growing familiarity with assisted reproduction techniques (ART) among pathogenic variant heterozygotes. We performed a retrospective multicenter study of PGT-M outcomes among French patients with genetic susceptibility to cancer. Our objectives were to collect data on this complex issue, and to help cancer geneticists counsel their patients of reproductive age. We also wanted to increase awareness regarding PGT-M among cancer genetics professionals. Pat...
Source: Familial Cancer - April 12, 2022 Category: Cancer & Oncology Source Type: research
Collaborative Group of the Americas on Inherited Gastrointestinal Cancers (CGA-IGC) Annual Virtual Meeting, November 13 –15, 2021
(Source: Familial Cancer)
Source: Familial Cancer - April 2, 2022 Category: Cancer & Oncology Source Type: research
Adaptation and early implementation of the PREdiction model for gene mutations (PREMM5 ™) 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 min or les...
Source: Familial Cancer - March 30, 2022 Category: Cancer & Oncology Source Type: research
