engleski

Potential indicators of melanoma predisposition in relatives of non-familial cases: alterations in CDKN2A locus in cutaneous melanoma

Aim:Constitutional alterations of CDKN2A/p16INK4A locususually cosegeregating within the family, was examined as a potential indicator of melanoma predisposition among the first-degree relatives of patients with malignant melanoma. Method: The study included eight families with a single member affected with melanoma. Members of the families were screened for allelic cosegregation with 9p21 region polymorphic markers IFNA, D9S126 and D9S104. The patient's tumors were screened for a loss of heterozygosity (LOH) with the same markers, as well as for single strand conformational polymorphism (SSCP) variability of CDKN2A. In suspected cases, constitutional DNA was examined by SSCP and direct sequencing. Results: LOH was detected in four cases, and SSCP indicated variability in at least one CDKN2A exon in these tumor samples. In three of four LOH cases, the remaining allele cosegregated within the family, which was interpreted as a preliminary indicator of potential genetic predisposition. In one of these three families, we found constitutional CDKN2A mutations in the patientand one of the relatives. In the second family, only the patient had the constitutionally altered gene, whereas no constitutional CDKN2A alterations were detected in the third family. All significant mutations were different and had not been reported before. Conclusion: We detected one case of melanoma predisposition among unaffected family members, which corresponded to stattistical expectations for such a small number of screened families. Since constitutional mutations of CDKN2A exons have limited incidence, our stepwise approach seemed to be more informative and more affordable than straight forward CDKN2A sequencing of all subjects.

alleles; genes; p16; genetic predisposition to disease; genectic screening; melanoma

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