Reduced Fhit expression in sporadic and BRCA2-linked breast carcinomas
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Agnarsson, B A
Sigbjornsdottir, B I
Kallioniemi, O P
Barkardottir, R B
Kovatich, A J
Hauck, W W
McCue, P A
MetadataShow full item record
CitationCancer Res. 1999, 59(11):2682-9
AbstractEvidence for alteration of the FHIT gene in a significant fraction of breast carcinomas has been reported, in apparent concordance with loss of heterozygosity (LOH) at chromosome region 3p14.2 in breast cancer and benign proliferative breast disease. A significantly higher frequency of LOH at the FHIT locus was reported for BRCA2-/- tumors, possibly due to misrepaired double-strand breaks at this common fragile region. To determine whether such genomic alterations lead to Fhit inactivation, we have assessed the level of Fhit expression by immunohistochemical detection in sporadic tumors and cancers occurring in BRCA2 999del5 carriers. To determine whether Fhit inactivation may have prognostic significance, we have also assessed expression of breast cancer markers and clinical features in sporadic tumors relative to Fhit expression. Of 40 consecutive sporadic breast carcinomas studied for tumor markers, 50% showed reduced Fhit expression. In these sporadic cancers, loss of Fhit expression was not correlated significantly with the presence or absence of other tumor markers. In a study of 58 sporadic and 34 BRCA2 999del5 Icelandic invasive cancers, there was a significant association of LOH at 3p14.2 with reduced expression of Fhit (P = 0.001); also the lower expression of Fhit and higher LOH at 3p14.2 in BRCA2 999del5 tumors relative to sporadic cancers was significant (P = 0.002). Thus, genetic alteration at the fragile site within the FHIT gene leads to loss of Fhit protein in a significant fraction of sporadic breast cancers and a much larger fraction of familial breast cancers with an inherited BRCA2 mutation, consistent with the idea that loss of BRCA2 function affects stability of the FHIT/FRA3B locus.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Analysis of the fragile histidine triad (FHIT) gene in lobular breast cancer.
- Authors: Huiping C, Jonasson JG, Agnarsson BA, Sigbjornsdottir BI, Huebner K, Ingvarsson S
- Issue date: 2000 Aug
- Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer.
- Authors: Yang Q, Nakamura M, Nakamura Y, Yoshimura G, Suzuma T, Umemura T, Shimizu Y, Mori I, Sakurai T, Kakudo K
- Issue date: 2002 Sep
- Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands.
- Authors: Ahmadian M, Wistuba II, Fong KM, Behrens C, Kodagoda DR, Saboorian MH, Shay J, Tomlinson GE, Blum J, Minna JD, Gazdar AF
- Issue date: 1997 Sep 1
- Chromosome imbalance at the 3p14 region in human breast tumours: high frequency in patients with inherited predisposition due to BRCA2.
- Authors: Bergthorsson JT, Johannsdottir J, Jonasdottir A, Eiriksdottir G, Egilsson V, Ingvarsson S, Barkardottir RB, Arason A
- Issue date: 1998 Jan
- Chromosome 8p alterations in sporadic and BRCA2 999del5 linked breast cancer.
- Authors: Sigbjörnsdottir BI, Ragnarsson G, Agnarsson BA, Huiping C, Barkardottir RB, Egilsson V, Ingvarsson S
- Issue date: 2000 May