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J M Hoang

Publications and source records attributed to J M Hoang.

9 recordsLinked to original sources
PubMed2001

Extensive characterization of genetic alterations in a series of human colorectal cancer cell lines.

A number of genetic alterations have been described in colorectal cancers. They include allelic losses on specific 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 different groups on different 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 different genetic alterations. We found significant correlations between mutational profiles in these colorectal cell lines associated with differences 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 different biological pathways involved in the development of colon cancer, and for groups studying cellular biology and pharmacology on the same cell lines.

Base Pair Mismatch↗
PubMed1998

Determination of the replication error phenotype in human tumors without the requirement for matching normal DNA by analysis of mononucleotide repeat microsatellites.

Microsatellite instability (MI) characterizing tumors with replication errors (RER+ tumors) was first described in colorectal tumors from hereditary non-polyposis colorectal cancer (HNPCC) patients as well as in sporadic cases. It has also been observed in subgroups of extracolonic sporadic tumors, but there is no consensus as to the number of microsatellite loci to examine, and the threshold percentage of unstable loci required to classify a tumor as RER+. We have recently shown that BAT-26, a mononucleotide repeat microsatellite, was quasi-monomorphic in DNA from normal individuals and from colorectal RER- samples, and showed important size variations in RER+ samples. In the present work, we analyzed BAT-26 allelic profiles in tumors of the breast (n = 107), brain (n = 78), stomach (n = 59), prostate (n = 49), esophagus (n = 36), thyroid (n = 31), endometrium (n = 12), and cervix (n = 10) whose RER status was already known, thus extending BAT-26 analysis to a total of 542 human solid tumors. BAT-26 alleles were quasi-monomorphic in RER- samples (475/481) and shortened in RER+ tumors (57/61), including four tumors shown to have been misclassified on the basis of dinucleotide repeat microsatellite analysis. In 3/481 RER- and 4/61 RER+ cases, BAT-26 size variation was important enough to attract attention, but not sufficient to establish the RER status of the corresponding tumors. In these cases, the analysis of BAT-25 and BAT-34C4, two other mononucleotide repeat microsatellites, was necessary to resolve the ambiguity. There were only 3 false positive cases. In conclusion, BAT-26 was able to identify the RER status of 539 out of 542 tumors from various origins (99.5% efficiency) in a single-step experiment without the requirement for matching normal DNA.

Breast Neoplasms↗
PubMed1997

Allelic profiles of mononucleotide repeat microsatellites in control individuals and in colorectal tumors with and without replication errors.

We have recently shown that analysis of BAT-26, was sufficient to establish the Replication Error status of colorectal tumors and cell lines without the need for matching normal DNA. BAT-26, a poly(A) tract in the 5th intron of the hMSH2 gene, does not present significant size variation either between the alleles of one individual or between alleles of different individuals. In colorectal tumors without defects in the replication error system (RER- phenotype), BAT-26 is also quasi-monomorphic. On the contrary, in RER+ colorectal tumors, BAT-26 shows unstable shortened alleles. In order to see whether this behaviour was specific for BAT-26, or was a more general phenomenon for mononucleotide repeat microsatellites, we analysed eight other mononucleotide repeats. In control individuals (72 samples) and in RER- colorectal tumors and cell lines (55 samples), these microsatellites were polymorphic, dimorphic, quasi-monomorphic or monomorphic, indicating that the quasi-monomorphic nature of BAT-26 was not a general rule. All of them showed a tendency to be shorter in RER+ colorectal tumors and cell lines (19 samples), but only quasi-monomorphic and monomorphic mononucleotide repeats could be used to determine the RER status of tumors without matching normal DNA, although with a lower efficiency than BAT-26 due to either a smaller range of shortening in RER+ tumors or to a larger number of false negative cases.

Alleles↗
PubMed1997

BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines.

Instability of microsatellites is a hallmark of the DNA replication error phenotype (RER+) due to the inactivation of mismatch repair genes. In humans, microsatellite instability has first been described in colorectal tumors developing in either hereditary nonpolyposis colorectal cancer or sporadic patients. Colorectal tumorigenesis in RER+ and RER- tumors is probably due to distinct mechanisms, and RER+ tumors have a better prognosis than RER- tumors. The study of the RER status of a tumor may thus be important in the future to determine biological prognosis factors and investigate therapeutical strategies. The RER status of 134 primary tumors and 26 cell lines derived from colorectal cancers was established by PCR amplification and analysis of a minimum of 32 microsatellite loci. This characterization allowed us to unambiguously classify 35 primary tumors and 7 cell lines as RER+. Typing of a single poly(A) tract, BAT-26, was sufficient to confirm the RER status of 159 of these 160 tumors and cell lines. Moreover, in DNA from unaffected individuals, normal tissues of a subset of the RER+ patients, and all RER- tumors or cell lines, BAT-26 was quasi-monomorphic, showing only minor size variations. BAT-26 alleles showing shortening from 4 to 15 bp were observed in all but 1 of the RER+ tumors and cell lines. The size difference between the range of normal large alleles and unstable small alleles was sufficient to be detected by electrophoresis on conventional polyacrylamide gels stained with ethidium bromide. We thus propose a simple, low-cost, and rapid method to screen for the RER status of colorectal cancer primary tumors and cell lines, even in the absence of matching normal DNA and, in most cases, without the need for radioactivity. This method could easily be set up in routine laboratories.

Alleles↗
PubMed1993

Repeat hepatectomy for cancer.

In a series of 279 hepatectomies performed for cancer between June 1984 and March 1992, 46 were repeat operations, for metastases in 41 patients. The primary tumour was in the colon and rectum (28 patients), APUDoma (five) and miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of patients who had recurrence after the first liver resection and in 40 per cent of those who had liver recurrence. An unsuspected extrahepatic recurrence was discovered and resected in eight instances and in two other cases a known extrahepatic recurrence was resected during the second hepatectomy. The hospital mortality rate was 2 per cent (one patient); the death was from nosocomial pneumonia. The total morbidity rate including minor complications was 32 per cent, with a higher frequency of haemorrhagic problems after secondary liver resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of postoperative complications after repeat hepatectomy was related significantly to operative blood loss greater than 1500 ml (P = 0.04). The technical problems of repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult in 67 per cent of second liver resections and 80 per cent of third procedures; (2) the liver parenchyma, which often had histological modifications between first and second resections and was more difficult to 'work' as shown by the mean duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min for primary liver resection); and (3) modification of the intraparenchymal vasculobiliary anatomy following liver regeneration after major hepatectomy. Intraoperative ultrasonography was of great benefit. Rates of crude and recurrence-free survival were relatively encouraging at 47 and 33 per cent 3 years after the second liver resection for the whole group. These values were lower for colorectal cancer (37 and 21 per cent 3 years after the second hepatectomy). These figures do not, however, convey the complete picture of the outcome for these patients. During the same follow-up period, 143 recurrences were detected and a mean of 2.9 resections per patient were performed. The indications for repeat hepatectomy are still to be clarified, although the surgical technique is safe.

Adult↗
PubMed1993

[Triple hepatectomy for cancer].

The resection of the metastases from digestive malignant lesions are always the most efficient treatment, if it is complete. However it must be performed without major operative risk. According to this point of view, it is logical to examine the feasibility of three successive hepatectomies for metastases. We report in this study our experience with five cases of triple hepatectomies performed for 4 colic cancers and 1 carcinoid cancer. Two major hepatectomies were performed during this third resection. The re-exposure of the liver was very difficult in 4 cases, and the texture of the liver parenchyma was flabby and abnormal in 5 cases (confirmed with the histologic study). The mean duration of the surgery was 307 minutes, the mean duration of the intermittent pedicle clamping was 59 minutes, and the mean blood loss was 1710 ml. No post-operative death occurred, and the morbidity was low. This 5 third hepatectomies have been compared, for the feasability, to the 41 second hepatectomies and to the 234 first hepatectomies which we have performed. In proportion as hepatectomies are carried out, the difficulties to expose the liver increase, the texture of the liver parenchyma gets spoiled and the duration of the operation increases. In conclusion, the third hepatectomies are technically difficult to perform, but they are feasable. However it is too early to be able to define their indications.

Adenocarcinoma↗