Kolorektale Tumorevolution bei chronisch-entzündlichen Darmerkrankungen

Hirsch, Daniela

doi:10.1007/s00292-019-00709-3

Pathologe

2019

DOI: 10.1007/s00292-019-00709-3

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Kolorektale Tumorevolution bei chronisch-entzündlichen Darmerkrankungen

Daniela Hirsch

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2021

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“…In other words, a significant proportion of the genomic evolution of a tumor may take place in histologically normal appearing tissue without histologic evidence of dysplasia. Compared to sporadic CRC, UC-CRCs are characterized by higher frequencies of TP53 mutations (70% vs. 61%) and lower frequencies of KRAS (34% vs. 43%) and APC mutations (12% vs. 81%) ( 15 – 19 ). TP53 mutations appear to be early events in UC-related colorectal carcinogenesis, in contrast to KRAS mutations, which have rarely been identified as founder events ( 20 , 21 ).…”

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confidence: 89%

Molecular characterization of ulcerative colitis-associated colorectal carcinomas

et al. 2021

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Patients with ulcerative colitis (UC) are at increased risk for developing colorectal cancer (CRC). In contrast to sporadic colorectal tumorigenesis, TP53 mutations occur early in the progression from inflamed colonic epithelium to dysplasia to CRC, and are sometimes readily detectable in inflamed, (yet) non-dysplastic mucosa. Here, we analyzed formalin-fixed paraffin-embedded tissue samples from 19 patients with long-standing UC (median 18 years, range 3 to 34) who had developed CRC as a consequence of chronic inflammation of the large bowel. We performed microsatellite instability testing, copy number analysis by array-based comparative genomic hybridization, mutation analysis by targeted next generation sequencing (48-gene panel) and TP53 immunostaining. The results were compared to The Cancer Genome Atlas (TCGA) data on sporadic CRC. All UC-CRC lesions in our cohort were microsatellite stable. Overall, genomic imbalances of UC-CRCs showed patterns of chromosomal aneuploidies characteristic for sporadic CRC with the exception of gains of chromosome arm 5p (12 of 23 UC-CRC, 52%), which are rare in sporadic CRCs from TCGA (21 of 144, 15%; FDR adjusted P = 0.006). UC-CRCs showed a predilection for TP53 alterations, which was the most frequently mutated gene in our cohort (20 of 23, 87%). Interestingly, spatially separated tumor lesions from individual patients tended to harbor distinct TP53 mutations. Similar to CRCs arising in a background of Crohn’s colitis, the genetic landscape of UC-CRCs was characterized by TP53 mutations and chromosomal aneuploidies including gains of chromosome arm 5p. Both alterations harbor the potential for early detection in precursor lesions, thus complementing morphologic diagnosis.

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Molecular characterization of ulcerative colitis-associated colorectal carcinomas

et al. 2021

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Kolorektale Tumorevolution bei chronisch-entzündlichen Darmerkrankungen

Cited by 1 publication

References 25 publications

Molecular characterization of ulcerative colitis-associated colorectal carcinomas

Molecular characterization of ulcerative colitis-associated colorectal carcinomas

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