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Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors

Krop, I ; Maguire, P ; Lahti-Domenici, J ; Lodeiro, G ; Richardson, A ; Johannsdottir, HK ; Nevanlinna, H ; Borg, Åke LU ; Gelman, R and Barkardottir, RB , et al. (2003) In Cancer Research 63(9). p.2024-2027
Abstract
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.... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
63
issue
9
pages
2024 - 2027
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000182640400006
  • pmid:12727813
  • scopus:0038743158
ISSN
1538-7445
language
English
LU publication?
yes
id
b7253e77-1d61-4c6e-bfdf-bde8cbdf1aa0 (old id 312186)
alternative location
http://cancerres.aacrjournals.org/cgi/content/abstract/63/9/2024
date added to LUP
2016-04-01 16:55:15
date last changed
2022-03-07 17:16:53
@article{b7253e77-1d61-4c6e-bfdf-bde8cbdf1aa0,
  abstract     = {{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 &lt; 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.}},
  author       = {{Krop, I and Maguire, P and Lahti-Domenici, J and Lodeiro, G and Richardson, A and Johannsdottir, HK and Nevanlinna, H and Borg, Åke and Gelman, R and Barkardottir, RB and Lindblom, A and Polyak, K}},
  issn         = {{1538-7445}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2024--2027}},
  publisher    = {{American Association for Cancer Research Inc.}},
  series       = {{Cancer Research}},
  title        = {{Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors}},
  url          = {{http://cancerres.aacrjournals.org/cgi/content/abstract/63/9/2024}},
  volume       = {{63}},
  year         = {{2003}},
}