Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Link Daniel C, Schuettpelz Laura G, Shen Dong, Wang Jinling, Walter Matthew J, Kulkarni Shashikant, Payton Jacqueline E, Ivanovich Jennifer, Goodfellow Paul J, Le Beau Michelle, Koboldt Daniel C, Dooling David J, Fulton Robert S, Bender R Hugh F, Fulton Lucinda L, Delehaunty Kimberly D, Fronick Catrina C, Appelbaum Elizabeth L, Schmidt Heather, Abbott Rachel, O'Laughlin Michelle, Chen Ken, McLellan Michael D, Varghese Nobish, Nagarajan Rakesh, Heath Sharon, Graubert Timothy A, Ding Li, Ley Timothy J, Zambetti Gerard P, Wilson Richard K, Mardis Elaine R
Аннотация
OBJECTIVE: To apply whole-genome sequencing to a patient without any significant family history of cancer but with suspected increased cancer susceptibility because of multiple primary tumors to identify rare or novel germline variants in cancer susceptibility genes. DESIGN, SETTING, AND PARTICIPANT: Skin (normal) and bone marrow (leukemia) DNA were obtained from a patient with early-onset breast and ovarian cancer (negative for BRCA1 and BRCA2 mutations) and therapy-related acute myeloid leukemia (t-AML) and analyzed with the following: whole-genome sequencing using paired-end reads, single-nucleotide polymorphism (SNP) genotyping, RNA expression profiling, and spectral karyotyping.
MAIN OUTCOME MEASURES: Structural variants, copy number alterations, single-nucleotide variants, and small insertions and deletions (indels) were detected and validated using the described platforms. RESULTS; Whole-genome sequencing revealed a novel, heterozygous 3-kilobase deletion removing exons 7-9 of TP53 in the patient's normal skin DNA, which was homozygous in the leukemia DNA as a result of uniparental disomy. In addition, a total of 28 validated somatic single-nucleotide variations or indels in coding genes, 8 somatic structural variants, and 12 somatic copy number alterations were detected in the patient's leukemia genome.
CONCLUSION: Whole-genome sequencing can identify novel, cryptic variants in cancer susceptibility genes in addition to providing unbiased information on the spectrum of mutations in a cancer genome.