Temporal stability and age-related prevalence of loss of imprinting of the insulin-like growth factor-2 gene.
BACKGROUND
Loss of genomic imprinting (LOI) of the insulin-like growth factor-2 gene (IGF2) is an epigenetic change involving abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 gene is found in tumor tissue, normal adjoining mucosa and peripheral blood lymphocytes (PBL) of some patients with colorectal cancer (CRC), suggesting that this alteration precedes and is a risk factor for CRC. However, whether LOI of IGF2 is transitory or remains a permanent epigenetic alteration is unknown.


RESULTS
Four-hundred patients, mean age 60.7 years (range 15-95), 287 (80%) Caucasian were studied. This included 210 (51.4%) patients with no colorectal neoplasia, and 190 (48.6) with colorectal neoplasia. LOI of IGF2 was present in all age strata examined, and no statistically significant association across age strata (p trend > 0.05) was noted. Forty-nine patients had repeat analysis of blood imprinting status at a mean follow up time of 38.2 +/- 12.9 months. All but three patients had the same imprinting status at follow up (94% agreement, kappa 0.79, p < 0.001). Genomic imprinting was stable for patients with and without colorectal neoplasia.


METHODS
Standard RT-PCR assays for imprinting analysis of IGF2 were performed on PBL from ApaI informative individuals recruited at baseline and repeated 1 to 3 years later. Prevalence of LOI of IGF2 was also evaluated according to age strata.


CONCLUSIONS
LOI of the IGF2 gene in PBL appears to be a stable epigenetic phenomenon in most patients. Furthermore, LOI of IGF2 was not associated with age, suggesting an inherited or congenital epigenetic event. These findings support the concept that LOI of IGF2 may be a useful risk factor for CRC predisposition.
Cruz-Correa
Marcia
M
Department of Medicine, University of Puerto Rico, San Juan, Puerto Rico, USA. marcia.cruz1@upr.edu
Zhao
Ronghua
R
Oviedo
Myriam
M
Bernabe
Raul D
RD
Lacourt
Mercedes
M
Cardona
Alberto
A
Lopez-Enriquez
Reynold
R
Wexner
Steven
S
Cuffari
Carmen
C
Hylind
Linda
L
Platz
Elizabeth
E
Cui
Hengmi
H
Feinberg
Andrew P
AP
Giardiello
Francis M
FM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008875:Middle Aged; D015995:Prevalence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
D007335:Insulin-Like Growth Factor II