Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors
(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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https://lup.lub.lu.se/record/312186
- author
- organization
- publishing date
- 2003
- 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 < 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}}, }