Malignant triton tumor in a patient with Li-Fraumeni syndrome and a novel TP53 mutation

We report a 3-year-old boy with a malignant triton tumor (MTT) involving the left masticator space with local invasion and regional lymph node metastasis. Family history and detection of a novel germline TP53 mutation confirmed his diagnosis of Li Fraumeni syndrome (LFS). MTT has not been previously described in association with LFS. This case along with a comprehensive review of the literature, illustrate the importance of both somatic and germline TP53 mutations in the pathogenesis MTT. The tumor could not be resected and he was successfully treated with intensive induction chemotherapy, irradiation, and high-dose chemotherapy with autologous stem cell transplantation. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35300/1/20700_fta.pd

Priority of Risk (But Not Perceived Magnitude of Risk) Predicts Improved Sun-Protection Behavior Following Genetic Counseling for Familial Melanoma

https://kent-islandora.s3.us-east-2.amazonaws.com/node/17927/87871-thumbnail.jpgBackground Understanding multiple components of risk perceptions is important because perceived risk predicts engagement in prevention behaviors. Purpose To examine how multiple components of risk perceptions (perceived magnitude of and worry about risk, prioritization of the management of one\u27s risk) changed following genetic counseling with or without test reporting, and to examine which of these components prospectively predicted improvements in sunprotection behavior 1 year later. Methods A prospective, nonrandomized study design was used. Participants were 114 unaffected members of melanoma-prone families who (i) underwent genetic testing for a CDKN2A/p16 mutation (n = 69) or (ii) were at comparably elevated risk based on family history and underwent genetic counseling but not testing (no-test controls, n = 45). Participants reported risk perception components and sun-protection behavior at baseline, immediately following counseling, and 1 month and 1 year after counseling. Results Factor analysis indicated three risk components. Carriers reported increased perceived magnitude and priority of risk, but not cancer worry. No-test controls showed no changes in any risk perception. Among noncarriers, priority of risk remained high at all assessments, whereas magnitude of risk and cancer worry decreased. Of the three risk components, greater priority of risk uniquely predicted improved self-reported sun protection 1 year post-counseling. Conclusions Priority of risk (i) seems to be a component of risk perceptions distinguishable from magnitude of risk and cancer worry, (ii) may be an important predictor of daily prevention behavior, and (iii) remained elevated 1 year following genetic counseling only for participants who received a positive melanoma genetic test result.</p

Pancreatic cancer as a sentinel for hereditary cancer predisposition

Background: Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) predisposition have been shown to play a role in pancreatic cancer susceptibility. Growing evidence suggests that pancreatic cancer may be useful as a sentinel cancer to identify families that could benefit from HBOC or CRC surveillance, but to date pancreatic cancer is only considered an indication for genetic testing in the context of additional family history. Methods: Preliminary data generated at the Huntsman Cancer Hospital (HCH) included variants identified on a custom 34-gene panel or 59-gene panel including both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer cases, unselected for family history. Given the strength of preliminary data and corresponding literature, 61 sequential pancreatic cancer cases underwent a custom 14-gene clinical panel. Sequencing data from HCH pancreatic cancer cases, pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to estimate the proportion of carriers with pathogenic and high probability of pathogenic variants of uncertain significance (HiP-VUS). Results: Approximately 8.6% of unselected pancreatic cancer cases at the HCH carried a variant with potential HBOC or CRC screening recommendations. A meta-analysis of unselected pancreatic cancer cases revealed that approximately 11.5% carry a pathogenic variant or HiP-VUS. Conclusion: With the inclusion of both HBOC and CRC susceptibility genes in a panel test, unselected pancreatic cancer cases act as a useful sentinel cancer to identify asymptomatic at-risk relatives who could benefit from relevant HBOC and CRC surveillance measures.United States National Institutes of Health (NIH) National Cancer Institute (NCI) [R01CA164138]; NCI [P30CA042014]; Utah Genome Project; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program; Government of Canada through Genome Canada; Canadian Institutes of Health Research; Ministere de l'enseignement superieur, de la recherche, de la science, et de la technologie du Quebec through Genome Quebec; NIH NCI Cancer Center Support Grant [P30CA042014]; Huntsman Cancer Foundation; National Human Genome Research Institute [T32HG008962]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood

Item does not contain fulltextHereditary gastrointestinal cancer predisposition syndromes have been well characterized, but management strategies and surveillance remain a major challenge, especially in childhood. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in care of children with a hereditary risk of cancer met to define surveillance strategies and management of children with cancer predisposition syndromes. In this article, we review the current literature in polyposis syndromes that can be diagnosed in childhood and may be associated with an increased incidence of gastrointestinal neoplasms and other cancer types. These disorders include adenomatous polyposis syndromes (APC and MUTYH), juvenile polyposis coli (BMPR1A and SMAD4), Peutz-Jeghers Syndrome (STK11/LKB1), and PTEN hamartoma tumor syndrome (PHTS; PTEN), which can present with a more limited juvenile polyposis phenotype. Herein, the panel of experts provides recommendations for clinical diagnosis, approach to genetic testing, and focus on cancer surveillance recommendations when appropriate during the pediatric period. We also review current controversies on genetic evaluation of patients with hepatoblastoma and indications for surveillance for this tumor. Childhood cancer risks and surveillance associated with disorders involving the mismatch repair genes, including Lynch syndrome and constitutional mismatch repair deficiency (CMMRD), are discussed elsewhere in this series. Clin Cancer Res; 23(13); e107-e14. (c)2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series

Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome

Abstract Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited condition caused by germline mutations of the TP53 tumor suppressor gene encoding p53, a transcription factor triggered as a protective cellular mechanism against different stressors. Loss of p53 function renders affected individuals highly susceptible to a broad range of solid and hematologic cancers. It has recently become evident that children and adults with LFS benefit from intensive surveillance aimed at early tumor detection. In October 2016, the American Association for Cancer Research held a meeting of international LFS experts to evaluate the current knowledge on LFS and propose consensus surveillance recommendations. Herein, we briefly summarize clinical and genetic aspects of this aggressive cancer predisposition syndrome. In addition, the expert panel concludes that there are sufficient existing data to recommend that all patients with LFS be offered cancer surveillance as soon as the clinical or molecular LFS diagnosis is established. Specifically, the panel recommends adoption of a modified version of the “Toronto protocol” that includes a combination of physical exams, blood tests, and imaging. The panel also recommends that further research be promoted to explore the feasibility and effectiveness of these risk-adapted surveillance and cancer prevention strategies while addressing the psychosocial needs of individuals and families with LFS. Clin Cancer Res; 23(11); e38–e45. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.</jats:p