Clinical and Molecular Features of Pediatric Cancer Patients With Lynch Syndrome

Authors

Sarah Scollon
Mohammad K Eldomery
Jacquelyn Reuther
Frank Y Lin
Samara L Potter
Lauren Desrosiers
Kenneth L McClain
Valeria Smith
Jack Meng-Fen Su
Rajkumar Venkatramani
Jianhong Hu
Viktoriya Korchina
Neda Zarrin-Khameh
Richard A Gibbs
Donna M Muzny
Christine Eng
Angshumoy Roy
D Williams Parsons
Sharon E Plon

Publication Date

11-1-2022

Journal

Pediatric Blood & Cancer

DOI

10.1002/pbc.29859

PMID

35713195

PMCID

PMC9529793

PubMedCentral® Posted Date

11-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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, Pediatric cancer, genomics, molecular, tumor profiling, Lynch syndrome

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.