title: Rarity of germline 1100delC mutation in CHK2 in patients with malignant melanoma of the skin.
abstract: In this study the proportion of sporadic and familial malignant melanoma (MM) cases harbouring 1100delC in CHK2 was determined to assess whether this mutation is associated with the occurrence of MM. Three groups of patients were studied: (i) 101 patients with histologically confirmed sporadic MM of the skin diagnosed in the city of Szczecin, Poland; (ii) 16 MM patients with a family history of MM in their first-degree relatives; and (iii) 1024 individuals selected at random by family doctors from the city of Szczecin. Molecular examination included an allele-specific oligonucleotide polymerase chain reaction assay for the CHK2 founder mutation (1100delC), genomic sequencing, loss of heterozygosity analysis using CA-repeat microsatellite markers, and haplotype analysis. The CHK2 founder mutation was detected in one out of 101 (1%) of the sporadic MM cases, in none of the 16 familial MMs, and in two of the 1024 individuals (0.2%) from the general population. The differences between the groups of patients were not statistically significant. The MM patient with a CHK2 founder mutation was a 56-year-old female with a history of brain tumours at age 33 and 40 years, sarcoma at 41 years and finally MM at 55 years. Examination of tumorous DNA isolated from the MM and the sarcoma from this patient revealed no loss of heterozygosity in either tumour. It seems that examination of sporadic or familial MM cases for the 1100delC germline mutation in CHK2 is not justified. To evaluate whether this CHK2 founder mutation is associated with MM in patients with LFS syndrome, more MM cases from LFS families should be examined.
authors.affiliation: Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin 70-111, Al. Powst. Wlkp. 72, Poland. debniak@wp.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Złowocka
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Maria
authors.initials: M
authors.lastname: Chosia
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases