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Lack of HIN-1 methy...
Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors
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Krop, I (author)
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Maguire, P (author)
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Lahti-Domenici, J (author)
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Lodeiro, G (author)
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Richardson, A (author)
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Johannsdottir, HK (author)
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Nevanlinna, H (author)
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- Borg, Åke (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Gelman, R (author)
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Barkardottir, RB (author)
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- Lindblom, A (author)
- Karolinska Institutet
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Polyak, K (author)
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(creator_code:org_t)
- 2003
- 2003
- English.
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In: Cancer Research. - 1538-7445 .- 0008-5472. ; 63:9, s. 2024-2027
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Krop, I
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Maguire, P
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Lahti-Domenici, ...
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Lodeiro, G
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Richardson, A
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Johannsdottir, H ...
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show more...
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Nevanlinna, H
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Borg, Åke
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Gelman, R
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Barkardottir, RB
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Lindblom, A
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Polyak, K
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Lund University
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Karolinska Institutet