Τίτλος:
Additional characterization of a hexanucleotide polymorphic site in the
first intron of human H-ras gene: comparative study of its alterations
in non-small cell lung carcinomas and sporadic invasive breast
carcinomas
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Intron 1 of the human I-I-l ns gene possesses a polymorphism consisting
of repetitions of the GGGCCT consensus. Three alleles have been reported
at this locus. We confirmed that two, pi and PZ, display four and two
repeats, respectively, with their internal sequence structure similar to
that previously described. The third, P3, previously assigned as a
three-unit repetition allele according to its electrophoretic mobility
and with no other information regarding its internal structure, was also
found. Sequence analysis of the P3 allele revealed that it consists of
three perfect repeats of the GGGCCT consensus. This polymorphism is
present only in human c-H-ras gene, although single hexanucleotide
repeats are found scattered within intron 1 of this gene in rodents.
Analysis of this locus in matched tumor/distant normal samples from. (i)
38 patients with nonsmall-cell lung carcinoma (NSCLC), and (ii) 35
patients with sporadic invasive breast carcinoma, revealed: (1) 6.6%
and 19% loss of heterozygosity (LOH) respectively, and (2) 10.5% and
2.9% hexanucleotide instability (III) respectively, detected by the
presence of shifted in length alleles. Shifted alleles exhibited altered
internal sequence structure in comparison to normal ones, suggesting
complex mutational events. The same pattern of alterations was also
detected in tissues adjacent to lung adenocarcinomas and dysplasias
adjacent to squamous cell carcinomas (7.7% LOH, 5.9% III), implying
that abnormalities at this locus may be early events in lung
carcinogenesis. The frequency of alterations (LOH vs. HI) was
significantly different among NSCLC and breast cancer (P=.005), probably
due to the different tumor biology of each system. Finally, altered mRNA
expression of H-ras gene was detected in all cases with HI, but this
finding was also observed in samples without I-II. In view of reports
showing that elements in intron 1 of H-ras gene potentially influence
its transcriptional regulation, from our results we cannot exclude that
the hexanucleotide locus could be an element with possible involvement
in expressional regulation of this gene. (C) 2001 Elsevier Science Tnc.
All rights reserved.
Συγγραφείς:
Kotsinas, A
Gorgoulis, VG
Zacharatos, P
Mariatos, G and
Kokotas, S
Liloglou, T
Ikonomopoulos, J
Zoumpourlis, V and
Kyroudi, A
Field, JK
Asimacopoulos, PJ
Kittas, C
Περιοδικό:
CANCER GENETICS AND CYTOGENETICS
Εκδότης:
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI:
10.1016/S0165-4608(00)00407-6
