TY - JOUR
T1 - Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors
AU - Krop, Ian
AU - Maguire, Paula
AU - Lahti-Domenici, Jaana
AU - Lodeiro, Gabriela
AU - Richardson, Andrea
AU - Johannsdottir, Hrefna Kristin
AU - Nevanlinna, Heli
AU - Borg, Ake
AU - Gelman, Rebecca
AU - Björk Barkardottir, Rosa
AU - Lindblom, Annika
AU - Polyak, Kornelia
PY - 2003/5/1
Y1 - 2003/5/1
N2 - We recently identified a candidate tumor suppressor gene, HIN-1, that is silenced due to methylation in the majority of sporadic breast carcinomas and is localized to 5q33-qter, an area frequently lost in BRCA1 tumors and thought to harbor a BRCA1 modifier gene. To establish whether germ-line mutations in HIN-1 may influence breast cancer risk, we sequenced the HIN-1 coding region in 10 familial breast cancer patients with positive logarithm of the odds scores of at least one of the markers flanking HIN-1. We also sequenced the HIN-1 coding region in 15 BRCA1 and 35 sporadic breast tumors to determine whether HIN-1 is the target of the frequent 5q loss in BRCA1 tumors. No sequence alterations were found in any of the cases analyzed. However, analysis of HIN-1 promoter methylation status revealed that in striking contrast to sporadic cases, there is a nearly complete lack of HIN-1 methylation in BRCA1 tumors (P < 0.0001). Sporadic breast tumors with a "BRCA1-like" histopathological phenotype also demonstrated significantly lower frequency of HIN-1 promoter methylation (P = 0.01) compared with other cancer types, and there was also a difference among tumors based on their estrogen receptor and HER2 status (P = 0.006), suggesting that HIN-1 methylation patterns are associated with specific breast cancer subtypes.
AB - We recently identified a candidate tumor suppressor gene, HIN-1, that is silenced due to methylation in the majority of sporadic breast carcinomas and is localized to 5q33-qter, an area frequently lost in BRCA1 tumors and thought to harbor a BRCA1 modifier gene. To establish whether germ-line mutations in HIN-1 may influence breast cancer risk, we sequenced the HIN-1 coding region in 10 familial breast cancer patients with positive logarithm of the odds scores of at least one of the markers flanking HIN-1. We also sequenced the HIN-1 coding region in 15 BRCA1 and 35 sporadic breast tumors to determine whether HIN-1 is the target of the frequent 5q loss in BRCA1 tumors. No sequence alterations were found in any of the cases analyzed. However, analysis of HIN-1 promoter methylation status revealed that in striking contrast to sporadic cases, there is a nearly complete lack of HIN-1 methylation in BRCA1 tumors (P < 0.0001). Sporadic breast tumors with a "BRCA1-like" histopathological phenotype also demonstrated significantly lower frequency of HIN-1 promoter methylation (P = 0.01) compared with other cancer types, and there was also a difference among tumors based on their estrogen receptor and HER2 status (P = 0.006), suggesting that HIN-1 methylation patterns are associated with specific breast cancer subtypes.
UR - http://www.scopus.com/inward/record.url?scp=0038743158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038743158&partnerID=8YFLogxK
M3 - Article
C2 - 12727813
AN - SCOPUS:0038743158
SN - 0008-5472
VL - 63
SP - 2024
EP - 2027
JO - Cancer Research
JF - Cancer Research
IS - 9
ER -