scholarly journals Predisposition to Pediatric and Hematologic Cancers: A Moving Target

Author(s):  
David Malkin ◽  
Kim E. Nichols ◽  
Kristin Zelley ◽  
Joshua D. Schiffman

Our understanding of hereditary cancer syndromes in children, adolescents, and young adults continues to grow. In addition, we now recognize the wide variation in tumor spectrum found within each specific cancer predisposition syndrome including the risk for hematologic malignancies. An increased understanding of the genetic mutations, biologic consequences, tumor risk, and clinical management of these syndromes will improve patient outcome. In this article, we illustrate the diversity of molecular mechanisms by which these disorders develop in both children and adults with a focus on Li-Fraumeni syndrome, hereditary paraganglioma syndrome, DICER1 syndrome, and multiple endocrine neoplasia syndrome. This is followed by a detailed discussion of adult-onset tumors that can occur in the pediatric population including basal cell carcinoma, colorectal cancer, medullary thyroid cancer, and adrenal cortical carcinoma, and the underlying hereditary cancer syndromes that these tumors could indicate. Finally, the topic of leukemia predisposition syndromes is explored with a specific focus on the different categories of syndromes associated with leukemia risk (genetic instability/DNA repair syndromes, cell cycle/differentiation, bone marrow failure syndromes, telomere maintenance, immunodeficiency syndromes, and transcription factors/pure familial leukemia syndromes). Throughout this article, special attention is made to clinical recognition of these syndromes, genetic testing, and management with early tumor surveillance and screening.

2015 ◽  
Vol 61 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Cristina Rossi Giacomazzi ◽  
Juliana Giacomazzi ◽  
Cristina B.O. Netto ◽  
Patricia Santos-Silva ◽  
Simone Geiger Selistre ◽  
...  

Summary Introduction: cancer is the second leading cause of death in children between the ages of 0 and 14 years, corresponding to approximately 3% of all cases diagnosed in Brazil. A significant percentage (5-10%) of pediatric cancers are associated with hereditary cancer syndromes, including Li-Fraumeni/Li-Fraumeni-like syndromes (LFS/LFL), both of which are caused by TP53 germline mutations. Recent studies have shown that a specific TP53 mutation, known as p.R337H, is present in 1 in 300 newborns in Southern and Southeast Brazil. In addition, a significant percentage of children with LFS/LFL spectrum tumors in the region have a family history compatible with LFS/LFL. Objective: to review clinical relevant aspects of LFS/LFL by our multidisciplinary team with focus on pediatric cancer. Methods: the NCBI (PubMed) and SciELO databases were consulted using the keywords Li-Fraumeni syndrome, Li-Fraumeni-like syndrome and pediatric cancer; and all manuscripts published between 1990 and 2014 using these keywords were retrieved and reviewed. Conclusion: although LFS/LFL is considered a rare disease, it appears to be substantially more common in certain geographic regions. Recognition of population- specific risks for the syndrome is important for adequate management of hereditary cancer patients and families. In Southern and Southeastern Brazil, LFS/ LFL should be considered in the differential diagnosis of children with cancer, especially if within the spectrum of the syndrome. Due to the complexities of these syndromes, a multidisciplinary approach should be sought for the counseling, diagnosis and management of patients and families affected by these disorders. Pediatricians and pediatric oncologists in areas with high prevalence of hereditary cancer syndromes have a central role in the recognition and proper referral of patients and families to genetic cancer risk evaluation and management programs.


Blood ◽  
2016 ◽  
Vol 128 (21) ◽  
pp. 2497-2503 ◽  
Author(s):  
Wendy Kohlmann ◽  
Joshua D. Schiffman

Abstract With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.


Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Wendy Kohlmann ◽  
Joshua D. Schiffman

Abstract With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.


2021 ◽  
Vol 41 (3) ◽  
pp. 218-228
Author(s):  
Rosario Ferrer‐Avargues ◽  
María Isabel Castillejo ◽  
Estela Dámaso ◽  
Virginia Díez‐Obrero ◽  
Noemí Garrigos ◽  
...  

2021 ◽  
pp. 1709-1718
Author(s):  
Kathleen F. Mittendorf ◽  
Sarah Knerr ◽  
Tia L. Kauffman ◽  
Nangel M. Lindberg ◽  
Katherine P. Anderson ◽  
...  

2016 ◽  
Vol 43 (1) ◽  
pp. 134-145 ◽  
Author(s):  
Farzana L. Walcott ◽  
Jigar Patel ◽  
Ronald Lubet ◽  
Luz Rodriguez ◽  
Kathleen A. Calzone

2016 ◽  
pp. 276-290
Author(s):  
Henry T. Lynch ◽  
Carrie L. Snyder ◽  
Jane F. Lynch

Thanks to the veritably logarithmic advances in the molecular genetics of many emerging hereditary cancer syndromes, genetic counselling has become of paramount importance. It is a key element of the emerging concepts for patient education and management, which have become the clinical bedrock for diagnosis and management of hereditary cancer. Genetic counsellors have become proficient in the understanding of the complexities of molecular genetics in relation to hereditary cancer syndromes, demonstrating their ability both to supplement and replace the customary physician’s role in this overall process. We have used colorectal cancer, in particular Lynch syndrome, as a clinical genetic model based on the authors’ experience with diagnosis, DNA testing, and counselling of thousands of families for over four decades. Undoubtedly, the surface of the proverbial iceberg has barely been grazed in regard to the developments for the genetic counseling discipline.


Sign in / Sign up

Export Citation Format

Share Document