Design, construction, and analysis of cell line arrays and tissue microarrays for gene expression analysis

Methods Mol Biol. 2011:784:139-53. doi: 10.1007/978-1-61779-289-2_10.

Abstract

Cell line array (CMA) and tissue microarray (TMA) technologies are high-throughput methods for analysing both the abundance and distribution of gene expression in a panel of cell lines or multiple tissue specimens in an efficient and cost-effective manner. The process is based on Kononen's method of extracting a cylindrical core of paraffin-embedded donor tissue and inserting it into a recipient paraffin block. Donor tissue from surgically resected paraffin-embedded tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in the recipient block. The representative area of interest is identified and circled on a haematoxylin and eosin (H&E)-stained section of the donor block. Using a predesigned map showing a precise spacing pattern, a high density array of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the recipient block using a tissue arrayer from Beecher Instruments. Depending on the depth of the cell line/tissue removed from the donor block 100-300 consecutive sections can be cut from each CMA/TMA block. Sections can be stained for in situ detection of protein, DNA or RNA targets using immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH), respectively. This chapter provides detailed methods for CMA/TMA design, construction and analysis with in-depth notes on all technical aspects including tips to deal with common pitfalls the user may encounter.

MeSH terms

  • Cell Line, Tumor
  • DNA / analysis*
  • Gene Expression Profiling / methods*
  • Humans
  • Immunohistochemistry
  • Neoplasms / genetics
  • Paraffin Embedding
  • RNA, Messenger / analysis*
  • Research Design
  • Tissue Array Analysis / methods*

Substances

  • RNA, Messenger
  • DNA