Genetic alterations during colorectal-tumor development Vogelstein B\', Fearon E

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Genetic alterations during colorectal-tumor development Vogelstein B', Fearon ER, Hamilton SR. Kerm SE, Preisinger AC, Leppert M. Nakamura Y, White R, Smits AM, Bos IL N Engl J Med. 1988 Sep 1:319(9):525-32 Abstract Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis Before you begin answering the questions make sure that you understand the following terms. arsing io the erthelial tseof e skn or of the The torero-a presence ce a nen, abnormal, grow???See r mferiol ogaas Neoplasia: Polyposis: Adenoma: ncogene: Histopathology:

Explanation / Answer

Answer 1 .a Mutation is the change in the nucleotide bases of a gene. This change of nucleotide base result in the different expression of gene and formation of different protein

b. Ras gene play an important role in cell signalling. When this gene get mutated, cell does not undergo apoptosis and keep on dividing and hence lead to carcinoma. Three important members of Ras gene family are HRAS, KRAS, NRAS.  

c. From mutation column, we get to know that single nucleotide bases in gene, Change the amino acid in protein. For example, in first mutation column, G is changed to A, that changes the amino acid from glycine to aspartic acid.  

2. According to table 1, class I adenoma, has the highest frequency of Ras mutation.

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