%0 Journal Article %1 Martelotto:2017:Nat-Med:28165479 %A Martelotto, L G %A Baslan, T %A Kendall, J %A Geyer, F C %A Burke, K A %A Spraggon, L %A Piscuoglio, S %A Chadalavada, K %A Nanjangud, G %A Ng, C K %A Moody, P %A D'Italia, S %A Rodgers, L %A Cox, H %A da Cruz Paula, A %A Stepansky, A %A Schizas, M %A Wen, H Y %A King, T A %A Norton, L %A Weigelt, B %A Hicks, J B %A Reis-Filho, J S %D 2017 %J Nat Med %K FFPE copy-number-variation fulltext single-cell %N 3 %P 376-385 %R 10.1038/nm.4279 %T Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608257/ %V 23 %X A substantial proportion of tumors consist of genotypically distinct subpopulations of cancer cells. This intratumor genetic heterogeneity poses a substantial challenge for the implementation of precision medicine. Single-cell genomics constitutes a powerful approach to resolve complex mixtures of cancer cells by tracing cell lineages and discovering cryptic genetic variations that would otherwise be obscured in tumor bulk analyses. Because of the chemical alterations that result from formalin fixation, single-cell genomic approaches have largely remained limited to fresh or rapidly frozen specimens. Here we describe the development and validation of a robust and accurate methodology to perform whole-genome copy-number profiling of single nuclei obtained from formalin-fixed paraffin-embedded clinical tumor samples. We applied the single-cell sequencing approach described here to study the progression from in situ to invasive breast cancer, which revealed that ductal carcinomas in situ show intratumor genetic heterogeneity at diagnosis and that these lesions may progress to invasive breast cancer through a variety of evolutionary processes.

@article{Martelotto:2017:Nat-Med:28165479, abstract = {A substantial proportion of tumors consist of genotypically distinct subpopulations of cancer cells. This intratumor genetic heterogeneity poses a substantial challenge for the implementation of precision medicine. Single-cell genomics constitutes a powerful approach to resolve complex mixtures of cancer cells by tracing cell lineages and discovering cryptic genetic variations that would otherwise be obscured in tumor bulk analyses. Because of the chemical alterations that result from formalin fixation, single-cell genomic approaches have largely remained limited to fresh or rapidly frozen specimens. Here we describe the development and validation of a robust and accurate methodology to perform whole-genome copy-number profiling of single nuclei obtained from formalin-fixed paraffin-embedded clinical tumor samples. We applied the single-cell sequencing approach described here to study the progression from in situ to invasive breast cancer, which revealed that ductal carcinomas in situ show intratumor genetic heterogeneity at diagnosis and that these lesions may progress to invasive breast cancer through a variety of evolutionary processes.}, added-at = {2017-10-03T11:05:41.000+0200}, author = {Martelotto, L G and Baslan, T and Kendall, J and Geyer, F C and Burke, K A and Spraggon, L and Piscuoglio, S and Chadalavada, K and Nanjangud, G and Ng, C K and Moody, P and D'Italia, S and Rodgers, L and Cox, H and da Cruz Paula, A and Stepansky, A and Schizas, M and Wen, H Y and King, T A and Norton, L and Weigelt, B and Hicks, J B and Reis-Filho, J S}, biburl = {https://www.bibsonomy.org/bibtex/20244f0cfea959df53b85c83e31538bc2/marcsaric}, description = {Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples}, doi = {10.1038/nm.4279}, interhash = {34736ef9d536005044abd6f2f2279125}, intrahash = {0244f0cfea959df53b85c83e31538bc2}, journal = {Nat Med}, keywords = {FFPE copy-number-variation fulltext single-cell}, month = mar, number = 3, pages = {376-385}, pmid = {28165479}, timestamp = {2017-10-03T13:48:19.000+0200}, title = {Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608257/}, volume = 23, year = 2017 }