Methods and probe combinations for detecting melanoma

A hybridization method comprising:

• a) contacting a sample of a skin lesion from a human subject with a combination consisting of four detectably labeled in situ hybridization probes, the four detectably labeled in situ hybridization probes consisting of a probe that selectively hybridizes to a target sequence within chromosome subregion 6p25, a probe that selectively hybridizes to a target sequence within chromosome subregion 6q23, a chromosome 6 enumerator probe that comprises a repetitive DNA sequence and selectively hybridizes to the centromeric or peri-centromeric region of chromosome 6, and an additional probe,
• wherein the additional probe is selected from the group consisting of a chromosome 10 enumerator probe that comprises a repetitive DNA sequence and selectively hybridizes to the centromeric or peri-centromeric region of chromosome 10, a probe that selectively hybridizes to a target sequence within chromosome subregion 7q34, a probe that selectively hybridizes to a target sequence within chromosome subregion 11q13, a probe that selectively hybridizes to a target sequence within chromosome subregion 17q25, and a probe that selectively hybridizes to a target sequence within chromosome subregion 20q13;
• and
• wherein the target sequence for each probe is from 70,000 nucleotides to 800,000 nucleotides, and each probe hybridizes along the entire length of its target sequence;
• b) incubating each probe of the combination with the skin lesion sample under in situ hybridization conditions in which each probe selectively hybridizes to its target sequence to form a stable hybridization complex, wherein each probe hybridizes to a lesser extent to, or not at all to non-target sequences, as compared to target sequences;
• and
• c) detecting hybridization of the combination of probes to determine copy number at any chromosome subregion to which the probes selectively hybridize,
• wherein the hybridization method employs no additional in situ hybridization probes beyond those in the combination.