bims-lifras Biomed News
on Li-Fraumeni Syndrome
Issue of 2019‒08‒25
six papers selected by
Joanna Zawacka-Pankau



  1. Cancer Sci. 2019 Aug 20.
    Fan Z, Hu L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xu Y, Xie Y.
      BRCA1/2 genes are the most frequently germline mutated DNA-repair genes and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non-BRCA1/2 DNA-repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA-repair genes were determined using a multigene panel in 7657 BRCA1/2-negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2-negative breast cancer patients, 257 (3.4%) carried at least one pathogenic germline mutation in the 16 DNA-repair genes. The prevalence of DNA-repair gene mutation was significant higher in familial breast cancers (5.2%, P=0.002) and early-onset breast cancers (diagnosed at and before age of 40) (4.5%, P=0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA-repair gene mutation carriers were significantly more likely to have a larger tumor (P=0.04) and axillary lymph-node metastasis (P=0.03). Moreover, DNA-repair gene mutation was an independent unfavorable factor for recurrence-free survival [adjusted hazard ratio (HR) =1.38, 95% CI: 1.00-1.91, P=0.05] and disease-specific survival (adjusted HR=1.63, 95% CI: 1.04-2.57, P=0.03) in this cohort. Overall, 3.4% of BRCA1/2-negative breast cancer patients carried germline mutations in the 16 DNA-repair genes, and the DNA-repair gene mutation carriers exhibited an aggressive phenotype and had a poor survival compared with noncarriers. This article is protected by copyright. All rights reserved.
    Keywords:  Breast cancer; Cancer susceptibility genes; DNA-repair genes; Germline mutation; Survival
    DOI:  https://doi.org/10.1111/cas.14175
  2. Genome Res. 2019 Aug 22.
    Edmonson MN, Patel AN, Hedges DJ, Wang Z, Rampersaud E, Kesserwan CA, Zhou X, Liu Y, Newman S, Rusch MC, McLeod CL, Wilkinson MR, Rice SV, Soussi T, Taylor JP, Benatar M, Becksfort JB, Nichols KE, Robison LL, Downing JR, Zhang J.
      Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.
    DOI:  https://doi.org/10.1101/gr.250357.119
  3. Clin Genet. 2019 Aug 21.
    Mathias S, Clément K, Meriem B, Mickael M, Chrystelle C, Florence C, Mélissa P, Philippe J, Olivier I, Sandra G, Louis M, Jérôme C, Angélique R, Marie M, Philippe L, Vinciane R, William G, Nadem S, Pascal H.
      The rate of genetic diagnosis of French patients with familial pancreatic ductal adenocarcinoma (PDAC) is not known. We report germline genetic testing data from 133 index cases meeting criteria for familial pancreatic cancer (FPC) as well as 87 "FPC-like" index cases who did not fulfilled strict FPC definition but were evocative for a PDAC predisposition. The overall rate of genetic diagnosis (in BRCA1, BRCA2, CDKN2A, and ATM genes) was 8.3% in FPC patients and 4.6% in FPC-like patients, consistent with the literature in other populations. Genetic variants were also identified in FANCA and BAP1 genes, as well as in the CDKN2A p12 transcript. This pancreas-specific transcript is a known key player in driving pancreatic oncogenesis. This might be the first described case of a PDAC genetic predisposition due to a variant in this specific transcript. This article is protected by copyright. All rights reserved.
    Keywords:  ATM; BAP1; Cancer genetics; FANCA; INK4a-ARF locus; familial pancreatic cancer
    DOI:  https://doi.org/10.1111/cge.13629
  4. Am J Manag Care. 2019 Aug;25(9 Spec No.): SP285-SP287
    Owens K, Schlager L, Welcsh PL.
      
  5. J Surg Oncol. 2019 Aug 21.
    Witt RG, Baldini EH, Raut CP.
      Soft tissue sarcomas (STS) are a rare and diverse group of tumors that affect both adult and pediatric populations. This review discusses current screening recommendations for populations at increased risk for STS, including those with genetic predispositions. We also review surveillance guidelines for those at risk for recurrence following curative-intent surgery.
    Keywords:  diagnostic screening programs; hereditary neoplastic syndromes; sarcoma; surveillance guidelines; surveillance imaging
    DOI:  https://doi.org/10.1002/jso.25676