Genetic analysis in a patient with nine primary malignant neoplasms: a rare case of Li-Fraumeni syndrome

Li,Xiaoyuan; Kang,Juan; Pan,Qi; Sikora-Wohlfeld,Weronika; Zhao,Dachun; Meng,Changting; Bai,Chunmei; Patwardhan,Anil; Chen,Richard; Ren,Hong; Butte,Atul J.; Ding,Keyue

doi:10.3892/or.2015.4501

Genetic analysis in a patient with nine primary malignant neoplasms: a rare case of Li-Fraumeni syndrome

Authors:
- Xiaoyuan Li
- Juan Kang
- Qi Pan
- Weronika Sikora-Wohlfeld
- Dachun Zhao
- Changting Meng
- Chunmei Bai
- Anil Patwardhan
- Richard Chen
- Hong Ren
- Atul J. Butte
- Keyue Ding
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Affiliations: Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education of China; Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China, Division of Systems Medicine, Department of Pediatrics, Stanford University, CA, USA, Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China, Personalis, Inc., Menlo Park, CA, USA
Published online on: December 21, 2015 https://doi.org/10.3892/or.2015.4501
Pages: 1519-1528

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Abstract

To identify rare mutations and retrospectively estimate the cancer risk of a 45-year old female patient diagnosed with Li-Fraumeni syndrome (LFS), who developed nine primary malignant neoplasms in a period of 38 years, we conducted next-generation sequencing in this patient. Whole-genome and whole-exome sequencing were performed in DNA of whole blood obtained a year prior to the diagnosis of acute myeloid leukemia (AML) and at the time of diagnosis of AML, respectively. We analyzed rare mutations in cancer susceptibility genes using a candidate strategy and estimated cancer risk using the Risk-O-Gram algorithm. We found rare mutations in cancer susceptibility genes associated with an increased hereditary cancer risk in the patient. Notably, the number of mutated genes in p53 signaling pathway was significantly higher than expected (p=0.02). However, the phenotype of multiple malignant neoplasms of the studied patient was unlikely to be caused by accumulation of common cancer risk alleles. In conclusion, we established the mutation profile in a rare case of Li-Fraumeni syndrome, illustrating that the rare mutations rather than the cumulative of common risk alleles leading to an increased cancer risk in the patient.

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