Autosomal Dominant Inheritance

Most hereditary cancer predisposition syndromes are inherited in an autosomal dominant pattern (Fig. 3-2). Humans have 46 chromosomes, arranged into 23 pairs. The first 22 pairs are called autosomes and are present in both males and females. The 23rd pair comprises the sex chromosomes, with females having two X chromosomes, and males having one X and one Y chromosome. The genes for most currently recognized hereditary cancer syndromes are located on the autosomes, meaning that

• Each child has a 50% chance of inheriting the mutation

• No "skipped generations"

• Equally transmitted by men and women qt<5~5_O Eh-i

Figure 3-2. Autosomal dominant inheritance. (From ASCO Curriculum: Cancer Genetics and Cancer Predisposition Testing, 2nd ed, 2004, Slide 1-40.)

rather than being sex-linked, they can be inherited and transmitted by both males and females. For this reason, it is important to consider both maternal and paternal family history when assessing cancer risk.

When a parent has a mutation in a hereditary cancer gene, he or she has one copy of the gene with the mutation and one copy without it. Each offspring of that individual inherits one copy of the parent's gene and thus a 50% chance of inheriting the copy with the mutation and a 50% chance of inheriting the copy without the mutation. A child of a mutation carrier who inherits the mutation can pass it on to future children. However, members of a family who are shown not to have a mutation previously identified in another relative cannot pass it to their offspring.

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