(a) Examples and (b) probable mechanism of LOH by mitotic recombination involving APC. (a) Illumina Beadstudio B allele frequency (upper) and Log R ratio plots from colorectal adenomas 3469-1-J-2 (breakpoint, 68–70 Mb) and 2079-L-AC-1 (66–69 Mb). CRC cell lines C170 (~79 Mb) and VACO4S (70–75 Mb) are shown for comparison. LOH is indicated by the splitting of the heterozygous calls around the B = 0.5 region. Note the copy number loss in 3469-1-J-2 at the mitotic recombination boundary, suggesting germline copy number variation or deletion of sequences as a result of recombination. (b) A highly simplified version of LOH by mitotic recombination. It is envisaged that a protein-truncating mutation in APC is present on one copy of chromosome 5. The other chromosome 5 then suffers a double strand break on its long arm proximal to APC. Rather than using a sister chromatid for repair (for example, if the break has not occurred during or after S phase), repair is effected (dashed line) using the other copy of chromosome 5 as a template. This causes the distal long arms of the two chromosome 5 s, including the APC mutation, to become genetically identical and hence LOH at APC occurs.