All cancer genomes carry somatic mutations. These include base substitutions, rearrangements, insertions and deletions (indels). Antibody suppliers have seen tremendous growth in the field of cancer research recently, with antibodies to at least 400 cancer genomes.
Driver mutations are direct somatic changes which confer an advantage for clonal growth and can lead to oncogenesis. Passengers or “silent mutations” do not lead to cancer development, but give important information on pre-cancerous cell changes. Epigenetic mutations do not alter the genetic code, but can still be passed on to at least one successive generation. All are of interest.
DNA damage, such as strand breaks, is common in normal cells, and most do not cause mutation. The changes are recognised by cell enzymes, and various DNA repair mechanisms, such as NER (nucleotide excision repair) correct the damage and prevent driver mutations occurring. Alternatives to repair include blocking of gene transcription and/or replication, resulting in cell death.
Certain agents damage the DNA structure by altering the base sequence during repair or replication. Once these mutations are present in both strands of the double helix they are no longer recognised as DNA damage by the cell, and may then start to replicate.
-Immunohistochemistry-Paraffin-NB500-704-img0002.jpg "Immunohistochemistry-Paraffin: ERCC1 Antibody")
NER is particularly associated with UV-activated DNA mutation. Bulky distortions in the double-helix activate removal of the lesion area, which is then repaired by replica DNA polymerase insertion or transcription-coupling. UV damage causes covalent links to form between dipyrimidine sequences and C-T mutations at CpG dinucleotides, thus disrupting DNA repair.
DNA mutations vary widely between cells, and so a cell-specific antibody catalogue would be an enormous advantage in the study of cancer. Recently a team was able to successfully catalogue the entire range of somatic mutations from a single melanoma cell-line. As well as reinforcing previous findings on UV mutation there was evidence of a new class of NER, deployed to both transcribed and non-transcribed sequences compared to intergenic DNA. It is hoped more single cell-lines will follow.
Novus Biologicals offers many NER reagents for your research needs including:
