Evidence map›Paper›PMID 41457833›Full record

ArticleCancer science2026

Genotype-Phenotype Correlations of Li-Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort.

Fumito Yamazaki, Yoshiko Nakano, Masashi Sanada, Hiroki Kurahashi, Shunsuke Miyai, Arisa Ueki, Yuko Watanabe, Daisuke Hasegawa, Shuhei Karakawa, Toshifumi Ozaki and 5 more

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In one paragraph

Article in Cancer science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Fumito YamazakiDepartment of Pediatrics, Keio University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0002-3579-634X
Yoshiko NakanoDepartment of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.ORCID https://orcid.org/0000-0001-5394-8194
Masashi SanadaDepartment of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan.
Hiroki KurahashiDivision of Molecular Genetics, Center for Medical Science, Fujita Health University, Toyoake, Japan.
Shunsuke MiyaiDivision of Molecular Genetics, Center for Medical Science, Fujita Health University, Toyoake, Japan.
Arisa UekiDepartment of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Yuko WatanabeDepartment of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
Daisuke HasegawaDepartment of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
Shuhei KarakawaDepartment of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
Toshifumi OzakiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Akira HirasawaDepartment of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.ORCID https://orcid.org/0000-0003-4124-5488
Akiko M SaitoClinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan.
Eisuke InoueShowa Medical University Research Administration Center, Showa Medical University, Tokyo, Japan.
Motohiro KatoDepartment of Pediatrics, The University of Tokyo, Tokyo, Japan.
Hiroyoshi HattoriDepartment of Clinical Genetics, NHO Nagoya Medical Center, Nagoya, Japan.ORCID https://orcid.org/0000-0002-1591-0192

Funding

AMED JP23ck0106857Kansai Medical UniversitySaitama Medical University
6 · The paper itself

Abstract

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term "attenuated LFS" has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as "LFS" in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype-phenotype correlations in several respects. UMIN-CTR: UMIN000045855.

Indexed as

Li-Fraumeni SyndromeTumor Suppressor Protein p53AdolescentAdultChildChild, PreschoolFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeGerm-Line MutationHumansInfantJapanMaleMutation, MissenseTP53 protein, humanTumor Suppressor Protein p53cancer predispositiongenotype–phenotype correlationshotspot variantsLi–Fraumeni syndromeTP53

Identifiers

PMID41457833
PMCPMC12951092

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.