Repetitive DNA alterations in human skin cancers.
Repetitive sequences constitute landmarks for genome regulation, evolution, and chromatin architecture. Patterns of specific and non-specific repetitive sequences change in many types and stages of tumor cells, characterized by band loss, gain, and (de) increased staining of pre-existing bands. In this work, repetitive DNA was studied in search of genome instability of skin cancers: basal and squamous cell carcinomas (BCC and SCC), malignant melanoma (MM), melanocytic nevus (MN), and actinic keratosis (AK) lesions. DNAs were extracted from blood and tumor samples from 21 BCC, 7 SCC, 11 MM and 7 lesions. Banding patterns were obtained by random amplification of polymorphic DNA (RAPD), and specific D9S50 and D9S52 microsatellites (9p21). D9S50 patterns revealed microsatellite instability (MSI) and/or loss of heterozygosity (LOH) in 36% BCC, 25% SCC, and 57% MM tumors. D9S52 microsatellite showed 28.5%; 42.8%; and 71.4% altered tumors, respectively. No microsatellite alterations were found in MN and AK. On the other hand, genomic rearrangements detected by RAPD were present in 100% tumors. In BCC, the mean number of tumor DNA alterations showed predominant gain of bands. On the contrary, MM samples presented loss, or decreased intensity signal of RAPD bands. Genome alterations in skin cancers would result from chromosomal rearrangements, aneuploidy and/or polysomies. The low-cost and quick RAPD technique may reveal unknown genes or DNA sequences associated with tumor development and progression, and may be easily implemented in clinical diagnosis.
Ribeiro
Gil R H
GR
Genetics Laboratory, Butantan Institute, Avenue Vital Brasil 1500, CEP 05503-900, São Paulo, SP, Brazil.
Francisco
Guilherme
G
Teixeira
Lúcia V S
LV
Romão-Correia
Rosana F
RF
Sanches
José A
JA
Neto
Cyro Festa
CF
Ruiz
Itamar R G
IR
D004273:DNA, Neoplasm / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D021141:Nucleic Acid Amplification Techniques; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012878:Skin Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm