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Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma

TitoloMolecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2016
AutoriConti, S., Gallo E., Sioletic S., Facciolo F., Palmieri G., Lauriola L., Evoli A., Martucci R., Di Benedetto A., Novelli Flavia, Giannarelli D., Deriu G., Granone P., Ottaviano M., Muti P., Pescarmona E., and Marino M.
RivistaJournal of Thoracic Disease
Volume8
Paginazione386-395
ISSN20721439
Parole chiaveadult, aged, article, clinical article, controlled study, disease course, disease severity, egfr gene, Female, fluorescence in situ hybridization, gene dosage, gene frequency, gene overexpression, gene sequence, genetic association, Genetic polymorphism, heterozygosity loss, homozygosity, human, immunohistochemistry, male, microsatellite marker, molecular genetics, oncogene, overall survival, prevalence, progression free survival, simple sequence repeat, thymoma
Abstract

Background: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. Results: We found two prevalent CA-SSR-1 genotypes: A homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: Shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Conclusions: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas. © Journal of Thoracic Disease.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84962171716&doi=10.21037%2fjtd.2016.02.40&partnerID=40&md5=0de344e317fe6c41f47cc49668cc3923
DOI10.21037/jtd.2016.02.40
Citation KeyConti2016386