Genomic profile of a Li-Fraumeni-like syndrome patient with a 45,X/46,XX karyotype, presenting neither mutations in TP53 nor clinical stigmata of Turner syndrome.
Li-Fraumeni syndrome (LFS) is a hereditary disorder that predisposes patients to several types of cancer and is associated with TP53 germline mutations. Turner syndrome (TS) is one of the most common aneuploidies in women. Patients with TS have a higher risk of developing cancer, although multiple malignant tumors are extremely rare. Herein, we describe a patient with a 45,X/46,XX karyotype with no classic phenotype of TS. She presented with a clinical diagnosis of Li-Fraumeni-like syndrome (LFL), showing papillary thyroid carcinoma and fibrosarcoma of the left flank, and had no TP53 germline mutations. Genome-wide analysis of copy number variations (CNVs) was assessed in DNA from peripheral blood cells and saliva. A total of 109 rare CNVs in the blood cells, including mosaic loss of the X chromosome (76% of cells), were identified. In saliva, three rare CNVs were detected, all of them were also detected in the blood cells: loss of 8q24.11 (EXT1), gain of 16q24.3 (PRDM7 and GAS8), and the mosaic loss of the X chromosome (50% of cells). Results of conventional G-banding confirmed the 45,X/46,XX karyotype. Surprisingly, the patient presented with an apparently normal phenotype. The PRDM and GAS8 genes are potential candidates to be associated with the risk of developing cancer in this LFL/TS patient.
International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil.
Tatiane R
TR
Basso
International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil.
Rolando A R
RA
Villacis
International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil.
Luisa M
LM
Canto
International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil.
Vinicius M F
VM
Alves
Department of Urology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.
Rainer M L
RM
Lapa
Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, Brazil.
Amanda F
AF
Nóbrega
Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, Brazil.
Maria I
MI
Achatz
International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil; Department of Urology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, Brazil. Electronic address: silvia.rogatto@cipe.accamargo.org.br.
Silvia R
SR
Rogatto
D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D041321:Chromosomes, Human, X / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D059785:Karyotype; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics
D003598:Cytoskeletal Proteins; C115742:GAS8 protein, human; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011495:Histone-Lysine N-Methyltransferase; C000602307:PRDM7 protein, human
Li-Fraumeni-like syndrome; Turner syndrome; genomic alterations; mosaicism