PT  - JOURNAL ARTICLE
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  - Barkardottir, Rosa Björk
AU  - Lindblom, Annika
AU  - Polyak, Kornelia
TI  - Lack of HIN-1 Methylation in BRCA1-linked and “BRCA1-like” Breast Tumors
DP  - 2003 May 01
TA  - Cancer Research
PG  - 2024--2027
VI  - 63
IP  - 9
4099  - http://cancerres.aacrjournals.org/content/63/9/2024.short
4100  - http://cancerres.aacrjournals.org/content/63/9/2024.full
SO  - Cancer Res2003 May 01; 63
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. ©2003 American Association for Cancer Research.