Allele-specific copy number analysis of tumors

Loo, Peter Van; Nordgard, Silje H.; Lingjærde, Ole Christian; Russnes, Hege G.; Rye, Inga Hansine; Sun, Wei; Weigman, Victor; Marynen, Peter; Zetterberg, Anders; Naume, Bjørn; Perou, Charles M.; Børresen-Dale, Anne Lise; Kristensen, Vessela N.

doi:10.1073/pnas.1009843107

Cited by 986 publications

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References 38 publications

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“…Analysis was performed in r (version 3.3.3). The tumor cell percentage in each sample was estimated from the SNP array data using the algorithm ASCAT (Allele‐Specific Copy number Analysis of Tumors) (Van Loo et al ., 2010). Abundance of stroma and immune cells in the samples was inferred from gene expression signatures by ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data; Yoshihara et al ., 2013).…”

Section: Methodsmentioning

confidence: 99%

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

et al. 2018

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The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer, particularly in the aggressive triple‐negative/basal‐like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor‐associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic resistance. In this study, we investigated the effect of the metastasis‐ and inflammation‐associated microenvironmental factor S100A4 on breast cancer cells (BCCs) of different subtypes and explored their further interactions with myeloid cells. We demonstrated that extracellular S100A4 activates BCCs, particularly the basal‐like subtype, to elevate secretion of pro‐inflammatory cytokines. The secreted factors promoted conversion of monocytes to TAM‐like cells that exhibited protumorigenic activities: stimulated epithelial–mesenchymal transition, proliferation, chemoresistance, and motility in cancer cells. In conclusion, we have shown that extracellular S100A4 instigates a tumor‐supportive microenvironment, involving a network of cytokines and TAM‐like cells, which was particularly characteristic for basal‐like BCCs and potentiated their aggressive properties. The S100A4–BCC–TAM interaction cascade could be an important contributor to the aggressive behavior of this subtype and should be further explored for therapeutic targeting.

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Section: Methodsmentioning

confidence: 99%

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

et al. 2018

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“…The ASCAT algorithm 43 was used to detect copy number aberrations and loss-of-heterozygosity regions in the tumor genome using Illumina Human-Omni1 SNP arrays.…”

Section: Methodsmentioning

confidence: 99%

Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing

et al. 2011

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“…SNP array hybridization on the Affymetrix SNP6.0 platform was as per Affymetrix Protocols. Copy number analysis was performed using ASCAT (version 2.1) accounting for nonneoplastic cell admixture and tumor aneuploidy (26) and resulted in integer allelespecific copy number profiles for the tumor cells. The data have been deposited in Array Express (E-MTAB-1141).…”

Section: Methodsmentioning

confidence: 99%

Whole exome sequencing of adenoid cystic carcinoma

Stephens¹,

Davies²,

Mitani³

et al. 2013

J. Clin. Invest.

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Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.

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Allele-specific copy number analysis of tumors

Cited by 986 publications

References 38 publications

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing

Whole exome sequencing of adenoid cystic carcinoma

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