Loss of heterozygosity at chromosome 9p21 (INK4-p14(ARF) locus): homozygous deletions and mutations in the p16 and p14(ARF) genes in sporadic primarymelanomas
R. Kumar et al., Loss of heterozygosity at chromosome 9p21 (INK4-p14(ARF) locus): homozygous deletions and mutations in the p16 and p14(ARF) genes in sporadic primarymelanomas, MELANOMA RE, 9(2), 1999, pp. 138-147
Loss of heterozygosity (LOH) was determined in 45 sporadic primary melanoma
s at six polymorphic microsatellite markers that flank the INK4a (p16-p14(A
RF)) locus on chromosome 9p21. We also determined allelic loss at two marke
rs on chromosome 9q and two markers at the Rb locus on chromosome 13, Homoz
ygous deletion of the p16 and p14(ARF) genes was determined by a fluorescen
t-based quantitative multiplex polymerase chain reaction method. LOH at one
or more polymorphic microsatellite markers on locus 9p21 was found in 32 o
f the melanomas (71%). The highest proportion of LOH was found at markers D
9S736 and D9S104, which are telomeric and centromeric to the INK4 locus, re
spectively. Five melanomas showed LOH at all the analysed markers located o
n chromosome 9p21. LOH at markers D9S942 and D9S974, which are located clos
e to the p16 and p14(ARF) genes, was found in 39% and 46% of melanomas, res
pectively. Analysis of the marker D9S257 on 9q22.1 showed LOH in 13 melanom
as (44% of the informative cases). A subset of melanomas with LOH at the IN
K4 locus also carried inactivating mutations within the p16 coding sequence
. Four melanomas carried homozygous deletions at the p16-p14(ARF) locus. Ou
r results suggest, besides the involvement of the INK4 locus in sporadic me
lanomas, the possibility of the existence of additional tumour suppressor l
oci on chromosome 9. (C) 1999 Lippincott Williams &,Wilkins.