title: A case of late-onset Li-Fraumeni-like syndrome with unilateral breast cancer.
abstract: Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yonggeun
authors.initials: Y
authors.lastname: Cho
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Jeong
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D003131:Combined Modality Therapy; D005091:Exons; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D008875:Middle Aged; D064847:Multimodal Imaging; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Breast cancer; LFL; LFS; Late onset; Li-Fraumeni syndrome; Li-Fraumeni-like syndrome; Penetrance; TP53