Title | Clinical and molecular features of pediatric cancer patients with Lynch syndrome. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Scollon, S, Eldomery, MK, Reuther, J, Lin, FY, Potter, SL, Desrosiers, L, McClain, KL, Smith, V, Su, JMeng-Fen, Venkatramani, R, Hu, J, Korchina, V, Zarrin-Khameh, N, Gibbs, RA, Muzny, DM, Eng, C, Roy, A, D Parsons, W, Plon, SE |
Journal | Pediatr Blood Cancer |
Volume | 69 |
Issue | 11 |
Pagination | e29859 |
Date Published | 2022 Nov |
ISSN | 1545-5017 |
Keywords | Brain Neoplasms, Child, Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair, DNA-Binding Proteins, Germ-Line Mutation, Humans, MutL Protein Homolog 1, MutS Homolog 2 Protein, Neoplastic Syndromes, Hereditary |
Abstract | BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD). PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies. RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second hits and/or increased tumor mutation burden in three of four patients with available tumor with potential implications for therapy and identification of at-risk family members. Only one patient met current guidelines for pediatric cancer genetics evaluation at the time of tumor diagnosis. CONCLUSION: Approximately 1% of children with cancer have Lynch syndrome, which is missed with current referral guidelines, suggesting the importance of adding MMR genes to tumor and hereditary pediatric cancer panels. Tumor analysis may provide the first suggestion of an underlying cancer predisposition syndrome and is useful in distinguishing between Lynch syndrome and CMMRD. |
DOI | 10.1002/pbc.29859 |
Alternate Journal | Pediatr Blood Cancer |
PubMed ID | 35713195 |
PubMed Central ID | PMC9529793 |
Grant List | U01 HG006485 / HG / NHGRI NIH HHS / United States |
Clinical and molecular features of pediatric cancer patients with Lynch syndrome.
Similar Publications
A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels. Blood. 2024;143(18):1845-1855. | .
Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology. Proc Natl Acad Sci U S A. 2024;121(19):e2322934121. | .
Exome sequencing implicates ancestry-related Mendelian variation at SYNE1 in childhood-onset essential hypertension. JCI Insight. 2024;9(9). | .