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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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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
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b7253e77-1d61-4c6e-bfdf-bde8cbdf1aa0 (old id 312186)
alternative location
http://cancerres.aacrjournals.org/cgi/content/abstract/63/9/2024
date added to LUP
2007-09-16 10:28:34
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2017-03-12 04:13:42
@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},
  volume       = {63},
  year         = {2003},
}