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

Author:
  • I Krop
  • P Maguire
  • J Lahti-Domenici
  • G Lodeiro
  • A Richardson
  • HK Johannsdottir
  • H Nevanlinna
  • Åke Borg
  • R Gelman
  • RB Barkardottir
  • A Lindblom
  • K Polyak
Publishing year: 2003
Language: English
Pages: 2024-2027
Publication/Series: Cancer Research
Volume: 63
Issue: 9
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1538-7445
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90