Lynch syndrome: further defining the pediatric spectrum

Self, Chelsea; Suttman, Alexandra; Schneider, Kami Wolfe; Hoffman, Lindsey M.

doi:10.1016/j.cancergen.2021.07.002

Cited by 12 publications

(13 citation statements)

References 11 publications

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“…Multigene panel testing and genetic counseling should then be considered for all patients with early-onset CRC given high likelihood and wide spectrum of mutations. [11][12][13] A polygenic etiology may be the cause of a virulent phenotype resulting in CRC earlier in life such as adolescence, as in our patients' cases. Outside of MMR genes, there are likely many unrecognized genetic or epigenetic factors that may influence the risk of developing malignancy in children and adolescents.…”

Section: Discussionmentioning

confidence: 74%

“…A recently published case series outlines seven pediatric patients with various pediatric malignancies, with subsequent diagnosis of LS. 11 It is important to acknowledge that LS and other hereditary polyposis syndromes can also occur in the setting of an initially negative family history as in Patient 1 and 3's case. In other pediatric polyposis syndromes, such as FAP and juvenile polyposis syndrome (JPS), roughly one-third of patients have no family history of the condition.…”

Section: Discussionmentioning

confidence: 99%

“…The first step in the evaluation of all pediatric patients with CRC should include microsatellite instability and immunohistochemistry staining of the tumor. Multigene panel testing and genetic counseling should then be considered for all patients with early‐onset CRC given high likelihood and wide spectrum of mutations 11–13 …”

Section: Discussionmentioning

confidence: 99%

“…Current guidelines recommend screening for LS for at‐risk patients at 20–25 years old or 5 years before the youngest age a relative was diagnosed; however, this case series among other reports highlight the need for earlier screening in at‐risk patients for both intestinal and extra‐intestinal cancer. A recently published case series outlines seven pediatric patients with various pediatric malignancies, with subsequent diagnosis of LS 11 …”

Section: Discussionmentioning

confidence: 99%

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Polygenic early‐onset colorectal cancer in pediatric patients

Phen

Berens

Moriarty

et al. 2022

Pediatric Blood & Cancer

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Colorectal cancer in the pediatric population is a rare but transpirable phenomenon.The occurrence should prompt suspicion for underlying genetic mutations in the setting of a hereditary cancer predisposition syndrome. In this series, we outline three pediatric patients with colonic adenocarcinoma who were found to have one or more germline mutations. The presence of compound mutations may lead to a hypermutator phenotype resulting in earlier presentation of colorectal cancer in childhood and adolescence. The diagnosis of colorectal cancer in pediatric patients warrants timely recognition, multigene panel testing, genetic counseling for the patient and family, and

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Polygenic early‐onset colorectal cancer in pediatric patients

Phen

Berens

Moriarty

et al. 2022

Pediatric Blood & Cancer

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“…The latter essentially includes Lynch syndrome, determined by monoallelic PV variants in the mismatch repair genes, which presents with a distinct phenotype from its biallelic form, the constitutional mismatch repair deficiency (CMMRD) syndrome [ 41 ]. LS is characterized by gastrointestinal and genitourinary malignancies that usually present in adult age, but with increasing reports of pediatric onset neoplasms [ 42 ].…”

Section: Classic Cancer Predisposition Syndromes and Clinical Phenoty...mentioning

confidence: 99%

Diagnostic Strategies and Algorithms for Investigating Cancer Predisposition Syndromes in Children Presenting with Malignancy

Rossini

Durante

Bresolin

et al. 2022

Cancers

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In the past recent years, the expanding use of next-generation sequencing has led to the discovery of new cancer predisposition syndromes (CPSs), which are now known to be responsible for up to 10% of childhood cancers. As knowledge in the field is in constant evolution, except for a few “classic” CPSs, there is no consensus about when and how to perform germline genetic diagnostic studies in cancer-bearing children. Several clinical screening tools have been proposed to help identify the patients who carry higher risk, with heterogeneous strategies and results. After introducing the main clinical and molecular features of several CPSs predisposing to solid and hematological malignancies, we compare the available clinical evidence on CPS prevalence in pediatric cancer patients and on the most used decision-support tools in identifying the patients who could benefit from genetic counseling and/or direct genetic testing. This analysis highlighted that a personalized stepwise approach employing clinical screening tools followed by sequencing in high-risk patients might be a reasonable and cost-effective strategy in the care of children with cancer.

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Molecular analysis of cancer genomes in children with Lynch syndrome: Exploring causal associations

Weijers,

Hirsch,

Bakhuizen

et al. 2024

Intl Journal of Cancer

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Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS‐spectrum (LSS) cancers, including high‐grade gliomas and colorectal cancer, causality has been supported by typical MMR‐related tumor characteristics, but for non‐LSS cancers, causality is unclear. We characterized 20 malignant tumors of 18 children with LS, including 16 non‐LSS tumors. We investigated second hits, tumor mutational load, mutational signatures and MMR protein expression. In all LSS tumors and three non‐LSS tumors, we detected MMR deficiency caused by second hit somatic alterations. Furthermore, these MMR‐deficient tumors carried driver variants that likely originated as a consequence of MMR deficiency. However, in 13 non‐LSS tumors (81%), a second hit and MMR deficiency were absent, thus a causal link between LS and cancer development in these children is lacking. These findings demonstrate that causality of LS in children with cancer, which can be determined by molecular tumor characterization, seems to be restricted to specific tumor types. Large molecular and epidemiological studies are needed to further refine the tumor spectrum in children with LS.

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Lynch syndrome: further defining the pediatric spectrum

Cited by 12 publications

References 11 publications

Polygenic early‐onset colorectal cancer in pediatric patients

Polygenic early‐onset colorectal cancer in pediatric patients

Diagnostic Strategies and Algorithms for Investigating Cancer Predisposition Syndromes in Children Presenting with Malignancy

Molecular analysis of cancer genomes in children with Lynch syndrome: Exploring causal associations

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