The Principles of Clinical Cytogenetics - Extra Materials - Springer

Chromosome Instability 353
Fig. 3. Sporadic (rows 1 and 2) and clonal (row 3) rearrangements in ataxia telangiectasia (R-banding).
Row 1, from left to right: inv(7)(p14q35), t(7;7)(p14;q35), t(14;14)(q11;q32), inv(14)(q11q32); row 2, from
left to right: t(7;14)(p14;q11), t(7;14)(q35;q11), t(7;14)(p14;q32), t(7;14)(q35;q32); row 3, from left to right:
inv(14)(q11;q32), t(X;14)(q28;q11) (note the late replicating X on the left ), t(14;14)(q11;q32). (Courtesy of
Alain Aurias and the Atlas of Genetics and Cytogenetics in Oncology and Haematology; modified figure
reprinted from ref. 33 with permission of the publisher, EDK.)
(see Fig. 3) are often seen in A-T lymphocytes. A greatly increased sensitivity of A-T cells to X-ray
and radiomimetic substances, such as bleomycin, is another characteristic cytogenetic hallmark. In a
study that utilized two recombination vectors, spontaneous intrachromosomal recombination rates
were 30–200 times higher in an A-T fibroblast line than in normal cells, but extrachromosomal recombination
frequencies were near normal (34). Therefore, the defects in ataxia telangiectasia seem to be
related primarily to the processes of DNA recombination, and increased recombination could contribute
to the high cancer risk seen in A-T patients. Repair deficiencies after ionizing irradiation are
secondary byproducts of such recombination defects. Nevertheless, treatment of malignancies with
conventional dosages of radiation can be fatal to A-T patients.
The presence of early-onset ataxia along with oculocutaneous telangiectasias facilitates a clinical
diagnosis of A-T, which can be problematic before the appearance of telangiectasias. The large size
of the ATM gene, together with the diversity and broad distributions of ATM gene mutations in A-T