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Genome remodelling in a basal-like breast cancer metastasis and xenograft.


ABSTRACT: Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

SUBMITTER: Ding L 

PROVIDER: S-EPMC2872544 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Genome remodelling in a basal-like breast cancer metastasis and xenograft.

Ding Li L   Ellis Matthew J MJ   Li Shunqiang S   Larson David E DE   Chen Ken K   Wallis John W JW   Harris Christopher C CC   McLellan Michael D MD   Fulton Robert S RS   Fulton Lucinda L LL   Abbott Rachel M RM   Hoog Jeremy J   Dooling David J DJ   Koboldt Daniel C DC   Schmidt Heather H   Kalicki Joelle J   Zhang Qunyuan Q   Chen Lei L   Lin Ling L   Wendl Michael C MC   McMichael Joshua F JF   Magrini Vincent J VJ   Cook Lisa L   McGrath Sean D SD   Vickery Tammi L TL   Appelbaum Elizabeth E   Deschryver Katherine K   Davies Sherri S   Guintoli Therese T   Lin Li L   Crowder Robert R   Tao Yu Y   Snider Jacqueline E JE   Smith Scott M SM   Dukes Adam F AF   Sanderson Gabriel E GE   Pohl Craig S CS   Delehaunty Kim D KD   Fronick Catrina C CC   Pape Kimberley A KA   Reed Jerry S JS   Robinson Jody S JS   Hodges Jennifer S JS   Schierding William W   Dees Nathan D ND   Shen Dong D   Locke Devin P DP   Wiechert Madeline E ME   Eldred James M JM   Peck Josh B JB   Oberkfell Benjamin J BJ   Lolofie Justin T JT   Du Feiyu F   Hawkins Amy E AE   O'Laughlin Michelle D MD   Bernard Kelly E KE   Cunningham Mark M   Elliott Glendoria G   Mason Mark D MD   Thompson Dominic M DM   Ivanovich Jennifer L JL   Goodfellow Paul J PJ   Perou Charles M CM   Weinstock George M GM   Aft Rebecca R   Watson Mark M   Ley Timothy J TJ   Wilson Richard K RK   Mardis Elaine R ER  

Nature 20100401 7291


Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was  ...[more]

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