title: Genetic analysis in a patient with nine primary malignant neoplasms: a rare case of Li-Fraumeni syndrome.
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.
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University, CA, USA.
authors.forename: Weronika
authors.initials: W
authors.lastname: Sikora-Wohlfeld
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Changting
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Bai
authors.affiliation: Personalis, Inc., Menlo Park, CA, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Patwardhan
authors.affiliation: Personalis, Inc., Menlo Park, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University, CA, USA.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: 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.
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
mesh_terms: D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53