High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays

Yuker Wang, Victoria Eh Carlton, George Karlin-Neumann, Ronald Sapolsky, Li Zhang, Martin Moorhead, Zhigang C. Wang, Andrea L. Richardson, Robert Warren, Axel Walther, Melissa Bondy, Aysegul Sahin, Ralf Krahe, Musaffe Tuna, Patricia A. Thompson, Paul Spellman, Joe Gray, Gordon Mills, Malek Faham

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Background. A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (∼40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Results. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE. Conclusion. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

Original languageEnglish (US)
Article number8
JournalBMC Medical Genomics
Volume2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Molecular Probes
Paraffin
Formaldehyde
Genotype
DNA
Technology
Neoplasms
Equidae
Tumor Cell Line

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Wang, Y., Carlton, V. E., Karlin-Neumann, G., Sapolsky, R., Zhang, L., Moorhead, M., ... Faham, M. (2009). High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays. BMC Medical Genomics, 2, [8]. https://doi.org/10.1186/1755-8794-2-8

High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays. / Wang, Yuker; Carlton, Victoria Eh; Karlin-Neumann, George; Sapolsky, Ronald; Zhang, Li; Moorhead, Martin; Wang, Zhigang C.; Richardson, Andrea L.; Warren, Robert; Walther, Axel; Bondy, Melissa; Sahin, Aysegul; Krahe, Ralf; Tuna, Musaffe; Thompson, Patricia A.; Spellman, Paul; Gray, Joe; Mills, Gordon; Faham, Malek.

In: BMC Medical Genomics, Vol. 2, 8, 2009.

Research output: Contribution to journalArticle

Wang, Y, Carlton, VE, Karlin-Neumann, G, Sapolsky, R, Zhang, L, Moorhead, M, Wang, ZC, Richardson, AL, Warren, R, Walther, A, Bondy, M, Sahin, A, Krahe, R, Tuna, M, Thompson, PA, Spellman, P, Gray, J, Mills, G & Faham, M 2009, 'High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays', BMC Medical Genomics, vol. 2, 8. https://doi.org/10.1186/1755-8794-2-8
Wang, Yuker ; Carlton, Victoria Eh ; Karlin-Neumann, George ; Sapolsky, Ronald ; Zhang, Li ; Moorhead, Martin ; Wang, Zhigang C. ; Richardson, Andrea L. ; Warren, Robert ; Walther, Axel ; Bondy, Melissa ; Sahin, Aysegul ; Krahe, Ralf ; Tuna, Musaffe ; Thompson, Patricia A. ; Spellman, Paul ; Gray, Joe ; Mills, Gordon ; Faham, Malek. / High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays. In: BMC Medical Genomics. 2009 ; Vol. 2.
@article{bda19f3fb7be4286947a508d0f2e9f48,
title = "High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays",
abstract = "Background. A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (∼40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Results. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88{\%} of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9{\%}), with only a modest loss in performance in FFPE. Conclusion. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.",
author = "Yuker Wang and Carlton, {Victoria Eh} and George Karlin-Neumann and Ronald Sapolsky and Li Zhang and Martin Moorhead and Wang, {Zhigang C.} and Richardson, {Andrea L.} and Robert Warren and Axel Walther and Melissa Bondy and Aysegul Sahin and Ralf Krahe and Musaffe Tuna and Thompson, {Patricia A.} and Paul Spellman and Joe Gray and Gordon Mills and Malek Faham",
year = "2009",
doi = "10.1186/1755-8794-2-8",
language = "English (US)",
volume = "2",
journal = "BMC Medical Genomics",
issn = "1755-8794",
publisher = "BioMed Central",

}

TY - JOUR

T1 - High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays

AU - Wang, Yuker

AU - Carlton, Victoria Eh

AU - Karlin-Neumann, George

AU - Sapolsky, Ronald

AU - Zhang, Li

AU - Moorhead, Martin

AU - Wang, Zhigang C.

AU - Richardson, Andrea L.

AU - Warren, Robert

AU - Walther, Axel

AU - Bondy, Melissa

AU - Sahin, Aysegul

AU - Krahe, Ralf

AU - Tuna, Musaffe

AU - Thompson, Patricia A.

AU - Spellman, Paul

AU - Gray, Joe

AU - Mills, Gordon

AU - Faham, Malek

PY - 2009

Y1 - 2009

N2 - Background. A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (∼40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Results. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE. Conclusion. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

AB - Background. A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (∼40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Results. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE. Conclusion. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

UR - http://www.scopus.com/inward/record.url?scp=63449110271&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63449110271&partnerID=8YFLogxK

U2 - 10.1186/1755-8794-2-8

DO - 10.1186/1755-8794-2-8

M3 - Article

C2 - 19228381

AN - SCOPUS:63449110271

VL - 2

JO - BMC Medical Genomics

JF - BMC Medical Genomics

SN - 1755-8794

M1 - 8

ER -