A number of genetic alterations have been described in colorectal cancers. They include allelic losses on speci®c chromosomal arms, mutations of oncogenes, tumor suppressor genes and mismatch repair genes, microsatellite instability in coding repeat sequences of target genes and methylation defects in gene promoters. Since these alterations have been reported by dierent groups on dierent tumors and cell lines, the complete repertoire of genetic alterations for any given tumor sample remains unknown. In the present study, we analysed a series of 22 colorectal cancer cell lines for 31 dierent genetic alterations. We found signi®cant correlations between mutational pro®les in these colorectal cell lines associated with dierences in mismatch repair status. This panel of colon cancer cell lines is representative of the genetic heterogeneity occurring in sporadic colorectal carcinoma. Our results may prove to be very useful for understanding the dierent biological pathways involved in the development of colon cancer, and for groups studying cellular biology and pharmacology on the same cell lines. Oncogene (2001) 20, 5025 ± 5032.

In the brain and the retina metabotropic glutamate receptors (mGluRs) modulate synaptic transmission; in particular, L-2-amino-4-phosphonobutyrate-sensitive group-III mGluRs are generally presynaptic and provide negative feedback of neurotransmitter release. We performed a comparative immunohistochemical analysis of the distribution of all group-III mGluRs in the mouse retina. mGluR6 expression was limited to the outer plexiform layer. Discrete, punctate immunolabeling, exclusively in the inner plexiform layer (IPL), was observed for each of the remaining group-III mGluRs. mGluR4 immunostaining was most abundant in IPL sublamina 1; mGluR7 immunoreactivity was organized in four bands, corresponding to sublaminae 1-4; and mGluR8 was localized in two broad bands, one each in the OFF and ON layers of the IPL. mGluR8 immunoreactivity was evident in the OFF plexus of cholinergic amacrine cell processes. Surprisingly, we found little overlap between group-III mGluR immunolabeling and that for the vesicular glutamate transporter VGLUT1. Instead, we found that mGluR4 and mGluR7 were located close to bipolar cell ribbons. No compensatory changes in the distribution of group-III mGluRs, or of several other markers also showing a stratified localization in the IPL, were observed in genetically engineered mice lacking either mGluR4, mGluR8, or both mGluR4 and mGluR8. The unique pattern of expression of each receptor suggests that they have distinct functions in the retina, and their asymmetric distribution in the ON and OFF layers of the IPL suggests distinct roles in the processing of light-ON and light-OFF stimuli.

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The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty-nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5-year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma. © 2002 Wiley-Liss, Inc.Key words: rectal carcinoma; p53 mutation; preoperative radiotherapy; radiosensitivity; survival Genetic alterations acquired during tumor progression can influence tumor behavior. In particular, mutations in the p53 tumorsuppressor gene have been implicated in tumor progression 1 and metastasis. 2 Inactivation of the p53 tumor-suppressor gene is found in approximately 50% of colorectal tumors 3 and appears to represent an independent prognostic factor of survival 4,5 whether patients were treated or not by adjuvant chemotherapy. Although both spontaneous evolution and modalities of rectal carcinoma treatment were significantly different from colonic carcinoma, rectal carcinomas were occasionally individualized from the different series that studied the interaction between p53 alterations and prognosis or response to therapy.In Europe, patients with rectal cancer tend to be treated by preoperative radiotherapy. 6,7 Therefore, determination of p53 status would be of specific clinical relevance for rectal cancers since p53 can influence the behavior of tumor cells submitted to ionizing radiation. 8 -20 To date, only 3 studies have evaluated the prognostic significance of p53 alterations in rectal cancer on patient survival and local tumor control after preoperative radiotherapy using immunohistochemistry. The conclusions concerning the association between p53 status and response to radiotherapy were inconsistent. [21][22][23] This discordance could be due to the methods used to detect p53 a...

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