MOLECULAR PATHOLOGY IN BASAL-CELL CANCER WITH P53 AS A GENETIC-MARKER

Citation
F. Ponten et al., MOLECULAR PATHOLOGY IN BASAL-CELL CANCER WITH P53 AS A GENETIC-MARKER, Oncogene, 15(9), 1997, pp. 1059-1067
Citations number
36
Categorie Soggetti
Oncology,Biology,"Cell Biology
Journal title
ISSN journal
09509232
Volume
15
Issue
9
Year of publication
1997
Pages
1059 - 1067
Database
ISI
SICI code
0950-9232(1997)15:9<1059:MPIBCW>2.0.ZU;2-D
Abstract
Human basal cell cancer (BCC) has unique growth characteristics with v irtual inability to metastasize, We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 mu m slices of tumors. From 11 BCC tumors 78 samples were analysed. Direct DIVA s equencing of exons 5-8 was performed, haplotypes were determined after cloning of p53 exons and loss of heterozygosity (LOH) ascertained by microsatellite analysis, All tumors had p53 mutations and in a majorit y both p53 alleles were affected, commonly through missense mutations. Microdissection of small parts (50-100 cells) of individual tumors sh owed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation, Samples from normal immunohistochemically negative epide rmis always showed wild type sequence, except for a case of previously unknown germline p53 mutation. Our analysis also included p53 immunor eactive patches i.e. morphologically normal epidermis with a compact p attern of p53 immunoreactivity. Mutations within those were never the same as in the adjacent BCC. This detailed study of only one gene thus uncovered a remarkable heterogeneity within a tumor category famous f or its benign clinical behavior.