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

Ian Krop, Paula Maguire, Jaana Lahti-Domenici, Gabriela Lodeiro, Andrea Richardson, Hrefna Kristin Johannsdottir, Heli Nevanlinna, Ake Borg, Rebecca Gelman, Rosa Björk Barkardottir, Annika Lindblom, Kornelia Polyak

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2024-2027
Number of pages4
JournalCancer Research
Volume63
Issue number9
StatePublished - May 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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