Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

Abstract

Neck lymphatic metastasis represents the single most important clinical prognostic factor in nasopharyngeal carcinoma (NPC), but underlying genetic mechanisms remain ill defined. In this study 23 samples of primary tumor (PT) and 9 of neck lymph node metastasis (NLNM) obtained from NPC patients were analyzed by comparative genomic hybridization (CGH) coupled with tissue microdissection and degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR). A similar pattern of chromosomal abnormalities was seen in PT and NLNM, the common aberrations were gains on 5p, 12p, 12q and 18p and deletions on 1p, 3p, 9q, 14q, 17p and 16q. However, NLNMs, but not PTs, also exhibited frequent losses on 9p, 16p, 17q, 20q, 21p, 21q and 22q and gains on 8q and 8p. The most frequent unique aberration in NLNMs was loss on 16p, observed in 100% (9/9) NLNMs tested, as well as loss of 20q, observed in 77.8% of tumors tested. For the first time, we report that a gain on 8p and a loss at 20q is common to NLNMs. The analysis furthermore suggests that specific alterations, e.g. losses of 9p, 16p, 7q, 20q, 21p, 21q, 22q and gains on 8q and 8p are associated with NLNM of NPC, and that these alterations may be involved in the onset and/or progression of a metastatic phenotype.

Allelic imbalance and abnormal expression of FHIT in endemic nasopharyngeal carcinoma: association with clinicopathological features

“…LOH is a loss of microsatellite allele at given loci implying genetic loss whereas MSI is represented by shifting of microsatellite bands which reflects replication error. Previous LOH studies confirmed the importance of chromosome 3p in NPC and indicated the role of TSGs on 3p in the development of NPC [1,3,18,19]. In this study, frequent LOH (70.7%) at FHIT gene locus was detected in NPC, and a positive association was observed between LOH and advanced-stage NPC.…”

“…LOH at the FHIT gene locus may be a late event contributing to tumorigenesis of this disease. Yan et al [18] have reported that chromosomal abnormalities were associated with neck nodal metastasis in NPC. The frequency of MSI at the FHIT gene region detected in this study (36.6%) was higher than previously reported (3.7%) [2].…”

High Micronucleus Frequency in Peripheral Blood Lymphocytes of Untreated Cancer Patients Irrespective of Gender, Smoking and Cancer Sites

“…Genetic instability was associated with the initiation and progresion of cancer in many reports (Yan et al 2005;Bonassi et al 2007); it ocurred mainly as the consequence of either missegregation of normal chromosomes or structural rearrangement (Muleris et al 2008) in both cancer cells as the target cells and peripheral lymphocytes as surrogate target cells . For years, lymphocytes can circulate through different organs accumulating DNA damages; therefore, chromosomal damages in lymphocytes are a relevant biomarker of health risk in humans (Lou et al 2007).…”

Loss of heterozygosity at chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas

“…Only few papers examined the status of allelic deletion of chromosome 14q in HNSCC. To the best of our knowledge, only three articles (two of them in nasopharynx cancers) reported allelic loss in cancer of the head and neck area (Lee et al 1997;Lung et al 2001;Yan et al 2005). In one of these articles, regions of 14q13-21 and 14q31-32.1 were indicated to be possibly harboring TSG (Lee et al 1997).…”

“…In one of these articles, regions of 14q13-21 and 14q31-32.1 were indicated to be possibly harboring TSG (Lee et al 1997). The other two reports related with nasopharyngeal cancer from China included only a few markers for analysis (Lung et al 2001;Yan et al 2005). Now we have a more precise mapping of each marker and gene and more accurate results for allelic deletion analysis.…”