Analysis of Loss of Heterozygosity for Tumor-Suppressor Genes Can Accurately Classify and Predict the Clinical Behavior of Mucinous Tumors Arising From the Appendix

Abstract

Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.

Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade

“…26 Our current, prospectively collected molecular data confirm the results from the previous study: highgrade mucinous adenocarcinomas (grades G2 and G3) more frequently accumulate allelic loss and mutational damage compared with low-grade (Grade G1) tumors. We found that the presence of high frequency LOH (fractional mutation rate Z25%) is also associated with poor survival.…”

“…Each sample was analyzed by 16 PCR reactions for individual polymorphic microsatellites situated at nine genomic regions (1p, 3p, 5q, 7q, 9p, 9q, 10q, 17p, and 18q) in proximity to tumor suppressor genes which have previously found to be mutated in patients with disseminated appendiceal mucinous neoplasms, as previously described. 26 The Genbank accession information for the microsatellite markers and cytogenetic localization are as follows: D1S407: 1p36.21; D1S171: 1p36; D3S1539: 3p26; D3S516: 3p26; D5S1384: 5q23; D5S615: 5q23; D7S486: 7q31; D7S1530: 7q31; D9S251: 9p21; D9S1748: 9p21; D9S252: 9q24; D10S520: 10q23; D10S1173: 10q23; D17S974: 17p13; D17S1289: 17p13; D18S487: 18q21. The PCR products were analyzed by capillary electrophoresis on an ABI 3130 (Applied Biosystems).…”

“…Allele peak heights and lengths were used to define the presence or absence of allelic loss imbalance, as previously described. 26 The fractional mutation rate was calculated for each sample and defined as the number of mutated markers divided by the total number of informative markers and expressed as a percent. A fractional mutation rate o25% was defined as low fractional mutation rate, whereas a fractional mutation rate Z25% was defined as high fractional mutation rate.…”

“…A fractional mutation rate o25% was defined as low fractional mutation rate, whereas a fractional mutation rate Z25% was defined as high fractional mutation rate. 26 …”

“…The fractional mutation rate is the proportion of chromosomal loci with allelic imbalance (LOH). 26 Data were available to calculate this metric in 141 patients (Table 4). Most cases (107/141, 76%) demonstrated a low fractional mutation rate.…”