Biomedical subjects

S C Jhanwar

Publications and source records attributed to S C Jhanwar.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Non random cytogenetic changes characterize Merkel cell carcinoma.

Merkel cell carcinoma is a rapidly proliferating neoplasm of neuroectodermal origin presenting in skin. Karyotypes obtained in direct preparations of three Merkel cell carcinomas were analyzed and compared with six other tumors which were reported in the literature. Of the nine tumors studied so far, eight (89 per cent) showed structural abnormalities of chromosome 1. These abnormalities were in the form of trisomy for chromosome 1q22----ter. Furthermore, it was also observed that the breaks of these rearrangements on chromosome 1 occurred at the bands to which c-oncogenes N-ras (p31), L-myc (p32), c-src (p36), c-ski (q22-22), and the beta-subunit of the nerve growth factor (NGF) (p22) were localized. In addition to structural changes, five out of the nine tumors (55.5 per cent) were trisomic for chromosome 1. Merkel cell tumors are often confused with small cell carcinoma of lung or peripheral neuroepithelioma. The cytogenetic abnormalities such as rearrangement of chromosome 3p and t(11;22)(q23;q12) which characterize lung carcinoma and peripheral neuroepithelioma, respectively, were not seen in any of the nine Merkel cell tumors studied. Thus it appears that rearrangement of chromosome 1 was non-randomly associated with Merkel cell carcinoma. It is of interest to note that genes involved in neuronal development and or differentiation have been mapped to the bands at which breaks occurred in these tumors. The significance of these changes is briefly discussed.

Aged↗

PubMedDate not supplied

Recurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal carcinoma: possible role in biological and clinical behavior of tumors.

We have employed cytogenetic and restriction fragment length polymorphism (RFLP) analysis to identify a full spectrum of cytogenetic and molecular alterations associated with initiation and progression of "sporadic" colorectal cancer and also to correlate the alterations with biological and clinical behavior of the tumors. The study series included 63 colorectal cancers, 47 primary and 16 metastatic recurrences. Cytogenetic analysis was successful in 48 tumors (76%) of which 44 (91%) were abnormal. Of these 44 tumors, clonal abnormalities were identified in 43, whereas chromosomes from one tumor were unsuitable for complete analysis. Each of these abnormal tumors displayed heterogeneity with regard to extent and complexity of recurrent chromosomal abnormalities. Numerical losses of chromosomes 17 and 18 (20-34%) and gains of chromosome 7 (28%) were significantly higher. The four most frequent structural rearrangements on the other hand, involved specific regions of chromosomes 1p, 5q, 17p, and 18q. The shortest regions of overlap of these rearrangements or losses were located at 1p36, 5q21-22, 17p13 and 18q21- > ter. RFLP analysis directed at 1p, 5q, 17p and 18q identified allelic deletions of these regions in 39 tumors (64%) which included 17 normal and 11 cytogenetic failures. Of all the informative tumors, 32%, 37%, 31%, and 63% showed allelic losses at chromosomes 1p, 5q, 17p and 18q respectively. The two methods of analysis (cytogenetics and RFLP) employed to identify genetic alterations were complementary; probes for chromosome 1 and 18 showed the greatest degree of concordance, whereas probes for chromosomes 5 and 17 provided relatively higher rate of discordance with cytogenetic results. These differences could be attributed mainly to three reasons: 1) a limited number of probes used for RFLP analysis; 2) contamination of tumor cells with normal cells, and 3) either mutational inactivation or deletion of specific alleles not closely linked to the probes used. Regardless of these limitations, however, the combined use of cytogenetic and RFLP identified genetic alterations in a large number of tumors and help elucidate the role of hyperdiploidy and/or relative deficiency of a given chromosomal segment in expression of recessive mutations. In addition, alterations of either chromosomes 1 or 17 predicted poorer survival for the patients with primary colorectal cancer (p = 0.03).

Blotting, Southern↗

PubMedDate not supplied

p53 mutations in colorectal cancers in the patients of Metropolitan New York.

An unselected series of 19 colorectal adenocarcinomas obtained from patients treated by surgery at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA was investigated for mutations in exons 5, 6, 7 and 8 of the p53 gene. Ten of the tumors revealed at least one somatic mutation either in the exon 5 or 8. Two of them were found to carry two somatic mutations each. The DGGE pattern of one of these two tumors indicated that it contained two different clonal cell populations; a similar assessment was not possible in the other tumor. Sequence analysis of all the observed variants showed that eighty percent of the mutations were due to transitions and that half of them were at mutational hot spot codons, 175 and 273.

Adenocarcinoma↗

PubMedDate not supplied

Expression of the retinoblastoma gene product in renal tumors.

BACKGROUND: Alterations in the retinoblastoma (Rb) gene and its protein product have been detected in numerous solid tumor malignancies. Loss of Rb function is believed to contribute to neoplastic transformation or to the development of metastases. To define the role of Rb in renal cancer, we analyzed renal tumor specimens for molecular alterations in the Rb gene and for lack of Rb protein expression, and correlated the results to clinicopathological characteristics. MATERIALS AND METHODS: Thirteen renal cancer cell lines, 62 primary renal tumors, and 5 metastatic renal cancers were studied by Southern blot analysis for defects in the Rb gene, and by immunohistochemistry for Rb protein expression. Results were correlated with histopathological parameters and patient survival. RESULTS: Structural alterations in the Rb gene were not detects in any of the renal cancer cell line or primary renal tumors studied. A rearranged Rb gene was observed in 1/5 metastatic tumor specimens. Western blot analyses revealed a truncated Rb protein in one of 13 renal cancer cell lines; immunohistochemical analysis revealed Rb protein in all papillary and oncocytic tumors, and in 39/44 non-papillary tumors. Rb expression patterns did not correlate with pathological stage, histological grade or the development of metastatic disease. CONCLUSION: Molecular alterations of the Rb gene are infrequent (<2%) in renal cancers, and Rb protein is present in the majority of primary (92%) and metastatic (100%) renal tumors. Loss of Rb expression does not appear to significantly contribute to malignant transformation or progression of renal cancers.

Adenocarcinoma↗