Biomedical subjects

Mario Hermsen

Publications and source records attributed to Mario Hermsen.

5 recordsLinked to original sources

PubMed2005

Centromeric chromosomal translocations show tissue-specific differences between squamous cell carcinomas and adenocarcinomas.

Structural chromosomal aberrations are common in epithelial tumors. Here, we compared the location of centromeric breaks associated with whole arm translocations in seven adenocarcinoma cell lines and nine squamous cell carcinoma cell lines using SKY, microarray-based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH). Whole arm translocations were more frequent in squamous cell carcinomas (112 in nine cell lines and nine in one short-term culture) than in adenocarcinomas (13 in seven cases) and most often resulted in copy number alterations. Array CGH analysis demonstrated that in all squamous cell carcinomas and in most adenocarcinomas, the breakpoints of unbalanced whole arm translocations occurred between the two clones on the array flanking the centromeres. However, FISH with centromeric probes revealed that in squamous cell carcinomas, the marker chromosomes with whole arm translocations contained centromeres comprised of material from both participating chromosomes, while in adenocarcinomas centromeric material from only one of the chromosomes was present. These observations suggest that different mechanisms of centromeric instability underlie the formation of chromosomal aberrations in adenocarcinomas and squamous cell carcinomas.

Adenocarcinoma↗

PubMed2005

Chromosomal changes in relation to clinical outcome in larynx and pharynx squamous cell carcinoma.

Invasive head and neck squamous carcinomas are among the cytogenetically most complex tumors. Perhaps for this reason, there is little consensus on the prognostic value of specific chromosomal aberrations. Here we present results of CGH analysis of 56 clinically well-characterized set of head and neck cancers, consisting of larynx and pharynx only. The aim was to find possible associations with clinical outcome. The major chromosome arms showing gains were (in decreasing order): 3q, 7q, 8q, 5p, 11q13, 17q and 18p, and losses occurred at 3p, 11qter, 4p, 18q, and 5q. The segments most frequently amplified were 3q26-qter, 11q13, 11q22, 3q12-13, 18p11.3, 18q11.2 and 8q24.3. Tumors with stages III and IV, and lymph node positive tumors had a worse clinical outcome. Surprisingly, no specific chromosomal abnormality correlated with disease-free survival. The only aberration that correlated to one of the clinico-pathological parameters was amplification 11q13, that occurred solely in lymph node positive, stage IV tumors. However 11q13 amplification did not correlate with disease-free survival. These results seem to indicate that genetic alterations at the level of chromosomes have limited prognostic value in patients with invasive larynx and pharynx squamous cell carcinomas.

Adult↗

PubMed2004

Comparative genomic hybridization in primary sinonasal adenocarcinomas.

BACKGROUND: Little is known about the genetic alterations that occur in sinonasal adenocarcinomas. The goal of the current study was to detect recurrent chromosomal gains and losses in a series of 21 primary sinonasal adenocarcinomas using comparative genomic hybridization (CGH). METHODS: The authors examined ethmoid sinus adenocarcinoma samples from 21 patients. All 21 adenocarcinomas were associated with work-related exposure to wood dust. CGH was used to detect chromosomal abnormalities, and the results of CGH analysis were evaluated for correlations with clinicopathologic characteristics. RESULTS: Chromosomal gains and losses were detected in all 21 adenocarcinomas. Gains were detected at high frequencies at 7q11-21 (n = 15 [71%]), 18p11 (n = 14 [66%]), 8q11-22 (n = 13 [62%]), 5p11-13 (n = 12 [57%]), 12q11-13 and 19p (n = 11 [52%]), 20q (n = 10 [47%]), X and 5p (n = 9 [43%]), and 3q26-27 (n = 8 [38%]); and losses were detected at 8p22-23 (n = 18 [86%]), 18q22-23 (n = 17 [80%]), 17p13 (n = 12 [57%]), and 5q31-qter (n = 11 [52%]). Aside from low-level gains, 43 high-level amplifications were observed in the current series of 21 tumors, most commonly at Xq13 (n = 7 [33%]). CONCLUSIONS: CGH revealed that ethmoid sinus adenocarcinomas carry a large number of chromosomal losses and gains, including high-level amplifications. To the authors' knowledge, the current study represents the first attempt to investigate sinonasal adenocarcinomas on a genetic level by using CGH. The pattern of chromosomal abnormalities in these tumors was different from the pattern in other tumors within the same anatomic region (e.g., squamous cell carcinomas and salivary gland tumors); this finding may be explained by differences in etiology. Nonetheless, sinonasal adenocarcinomas appear to be genetically similar to adenocarcinomas of the stomach and colon, which also have an etiology that differs from that of sinonasal adenocarcinomas. Further study is necessary to better understand the molecular genetic basis underlying the development of sinonasal adenocarcinomas. In the near future, this type of understanding may present new possibilities for prevention and treatment of malignant disease.

Adenocarcinoma↗

PubMed2003

LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21.

Recently, the gene PTPRJ (protein tyrosine phosphatase receptor type J) was identified as the candidate gene for the mouse colon cancer susceptibility locus Scc1. Its human homologue PTPRJ is frequently deleted in several cancer types, including colorectal cancer. To elucidate the role of PTPRJ loss in different stages of colorectal cancer and in its pathways of progression, we expanded the previously published comparative genomic hybridization results with novel data on loss of heterozygosity (LOH) at the PTPRJ locus. We identified a strong association between the LOH of PTPRJ and the loss of chromosomal region 18q12-21 (P=0.009). This observation is specific for progressed colorectal adenomas, suggesting that an interaction between LOH of PTPRJ and loss of 18q12-21 may be involved in the development of a more progressed form of adenomas.

Adenoma↗

PubMed2002

Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability.

BACKGROUND & AIMS: Current models of colorectal adenoma to carcinoma progression do not fully reflect the genetic heterogeneity and complexity of the disease. The aim of the present study was to identify genetic changes discriminating adenomas that have progressed to carcinoma from adenomas that have not progressed, and to refine the current genetic models of colorectal adenoma to carcinoma progression, based on a genome-wide analysis of chromosomal aberrations. METHODS: Sixty-six nonprogressed colorectal adenomas, 46 progressed adenomas (malignant polyps), and 36 colorectal carcinomas were screened for chromosomal aberrations by comparative genomic hybridization, and for mutations in the adenomatous polyposis coli (APC) and K-ras gene. Data analysis focused on cancer-associated genetic changes in adenomas. RESULTS: Accumulation of losses in 8p21-pter, 15q11-q21, 17p12-13, and 18q12-21, and gains in 8q23-qter, 13q14-31, and 20q13 were strongly associated with adenoma-to-carcinoma progression, independent of the degree of dysplasia. Hierarchic cluster analysis demonstrated the presence of 3 distinct subgroups of adenomas, characterized by unique combinations of genetic aberrations in the adenomas (17p loss and K-ras mutation, 8q and 13q gain, and 18q loss and 20q gain, respectively). CONCLUSIONS: The presence of 2 or more of the aforementioned 7 chromosomal changes was associated with progressed colorectal adenomas and colorectal cancer. In addition, evidence was found that these chromosomal abnormalities occurred in specific combinations of a few abnormalities rather than as a mere accumulation of events, indicating the existence of multiple independent chromosomal instability pathways of colorectal cancer progression.

Adenoma↗