Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

Abstract

SummaryThe distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30-64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35-p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis.

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

“…At chromosome 1, LOH at 1p31 has been associated with survival [13] supported by our findings of 1p31-21 downregulated in metastasizing breast tumors. At 1q an early LOH study found association to 1q21 [14] and CGH has been used to demonstrate prognostic disadvantage of simultaneously gain of 1q and 8q [15].…”

Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients

“…Together with another tumor showing an interstitial ampli®cation on 1p22 ± q22, the minimal region of ampli®cation could be ascertained to the 1q21 ± q22 band. In the last decade, molecular genetic studies have mainly focused on losses a ecting the distal part of chromosome 1p, since this latter region is suspected to contain a tumor suppressor gene in neuroblastoma and many other solid neoplasia (Ragnarsson et al, 1999). However, in light of recent evidence (Arribas et al, 1999) and the present study, it appears that gains of chromosome 1q are far more prevalent than, and frequently disconnected from 1p loss in HCC.…”

Evidence that MIG-6 is a tumor-suppressor gene

“…Allelic imbalance of chromosome 1p36 is one of the most frequent genetic alterations observed in various human cancers (Ragnarsson et al, 1999;Thiagalingam et al, 2002). Linkage analyses using microsatellite markers revealed deletions of 1p36 in nearly 50% of primary human lung cancers (Nomoto et al, 2000).…”