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- W3200619043 abstract "ABSTRACT High-grade serous ovarian cancer (HGSOC) originates in the fallopian tube epithelium and is characterized by ubiquitous TP53 mutation and extensive chromosomal instability (CIN). However, direct causes of CIN, such as mutations in DNA replication and mitosis genes, are rare in HGSOC. We therefore asked whether oncogenic mutations that are common in HGSOC can indirectly drive CIN in non-transformed human fallopian tube epithelial cells. To model homologous recombination deficient HGSOC, we sequentially mutated TP53 and BRCA1 then overexpressed MYC. Loss of p53 function alone was sufficient to drive the emergence of subclonal karyotype alterations. TP53 mutation also led to global gene expression changes, influencing modules involved in cell cycle commitment, DNA replication, G2/M checkpoint control and mitotic spindle function. Both transcriptional deregulation and karyotype diversity were exacerbated by loss of BRCA1 function, with whole-genome doubling events observed in independent p53/BRCA1-deficient lineages. Thus, our observations indicate that loss of the key tumour suppressor TP53 is sufficient to deregulate multiple cell cycle control networks and thereby initiate CIN in pre-malignant fallopian tube epithelial cells. This article has an associated First Person interview with the first author of the paper." @default.
- W3200619043 created "2021-09-27" @default.
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- W3200619043 date "2021-11-01" @default.
- W3200619043 modified "2023-10-16" @default.
- W3200619043 title "<i>TP53</i> loss initiates chromosomal instability in fallopian tube epithelial cells" @default.
- W3200619043 cites W1254790682 @default.
- W3200619043 cites W1483473129 @default.
- W3200619043 cites W1602927283 @default.
- W3200619043 cites W1758302002 @default.
- W3200619043 cites W1965761427 @default.
- W3200619043 cites W1970442105 @default.
- W3200619043 cites W1971465366 @default.
- W3200619043 cites W1981652313 @default.
- W3200619043 cites W1981974167 @default.
- W3200619043 cites W1999574084 @default.
- W3200619043 cites W2010457001 @default.
- W3200619043 cites W2016661249 @default.
- W3200619043 cites W2021341670 @default.
- W3200619043 cites W2030649154 @default.
- W3200619043 cites W2031211461 @default.
- W3200619043 cites W2036897871 @default.
- W3200619043 cites W2042231416 @default.
- W3200619043 cites W2061848287 @default.
- W3200619043 cites W2071014344 @default.
- W3200619043 cites W2071855640 @default.
- W3200619043 cites W2081098333 @default.
- W3200619043 cites W2084833108 @default.
- W3200619043 cites W2086887940 @default.
- W3200619043 cites W2088179903 @default.
- W3200619043 cites W2089477889 @default.
- W3200619043 cites W2096465161 @default.
- W3200619043 cites W2097933346 @default.
- W3200619043 cites W2102502996 @default.
- W3200619043 cites W2103726956 @default.
- W3200619043 cites W2107665951 @default.
- W3200619043 cites W2108643617 @default.
- W3200619043 cites W2111900617 @default.
- W3200619043 cites W2117649404 @default.
- W3200619043 cites W2123696077 @default.
- W3200619043 cites W2130410032 @default.
- W3200619043 cites W2133646845 @default.
- W3200619043 cites W2135780800 @default.
- W3200619043 cites W2137526110 @default.
- W3200619043 cites W2152602151 @default.
- W3200619043 cites W2159707944 @default.
- W3200619043 cites W2161577298 @default.
- W3200619043 cites W2167869412 @default.
- W3200619043 cites W2169456326 @default.
- W3200619043 cites W2170725518 @default.
- W3200619043 cites W2265772272 @default.
- W3200619043 cites W2343436177 @default.
- W3200619043 cites W2411962548 @default.
- W3200619043 cites W2414771725 @default.
- W3200619043 cites W2465420247 @default.
- W3200619043 cites W2476874854 @default.
- W3200619043 cites W2574604975 @default.
- W3200619043 cites W2608835133 @default.
- W3200619043 cites W2691929059 @default.
- W3200619043 cites W2693925639 @default.
- W3200619043 cites W2764321027 @default.
- W3200619043 cites W2767122952 @default.
- W3200619043 cites W2767326431 @default.
- W3200619043 cites W2775258968 @default.
- W3200619043 cites W2795441313 @default.
- W3200619043 cites W2797725119 @default.
- W3200619043 cites W2803674635 @default.
- W3200619043 cites W2884903585 @default.
- W3200619043 cites W2896800728 @default.
- W3200619043 cites W2901306165 @default.
- W3200619043 cites W2917933808 @default.
- W3200619043 cites W2953270703 @default.
- W3200619043 cites W2964724689 @default.
- W3200619043 cites W2974376001 @default.
- W3200619043 cites W2986915805 @default.
- W3200619043 cites W2990742618 @default.
- W3200619043 cites W3001572379 @default.
- W3200619043 cites W3006255103 @default.
- W3200619043 cites W3011143761 @default.
- W3200619043 cites W3015375987 @default.
- W3200619043 cites W3031036292 @default.
- W3200619043 cites W3045523221 @default.
- W3200619043 cites W3083387679 @default.
- W3200619043 cites W3090251225 @default.