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Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.

Castagnola P, Zoppoli G, Gandolfo S, Monticone M, Malacarne D, Cirmena G, Brown D, Aiello C, Maffei M, Marino R, Giaretti W, Pentenero M - PLoS ONE (2015)

Bottom Line: Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM.Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains.Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

View Article: PubMed Central - PubMed

Affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.

ABSTRACT
Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

No MeSH data available.


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Relationship between total CNAs and histological diagnosis in TNG and BM OPMDs/OSCCs.(A) shows the number of total CNAs detected in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) in tongue (TNG) and buccal mucosa (BM) sites; (B) shows the number of total CNAs detected in non-dysplastic OPMDs (ND-OPMDs) in TNG and BM sites. (C) shows the number of total CNAs detected in dysplastic OPMDs (D-OPMDs) and OSCC TNG and BM sites. The bottom and the top of each box show the first and third quartile while the line inside the box represents the median (second quartile). Please notice that when the median is not shown, its value = 0. The tips of the whiskers represent the minimum and the maximum data value. CNAs are referred to as: total focal gains, TFG; total broad gains, TBG; total focal losses, TFL; total broad losses, TBL. Broad gains and broad losses correspond to gains or losses of more than half a chromosome arm, respectively. The boxes corresponding to the number of CNAs detected in TNG OPMDs/OSCCs are shown in white bars, whereas those of CNAs detected in BM OPMDs/OSCCs are shown in gray bars.
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pone.0142294.g005: Relationship between total CNAs and histological diagnosis in TNG and BM OPMDs/OSCCs.(A) shows the number of total CNAs detected in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) in tongue (TNG) and buccal mucosa (BM) sites; (B) shows the number of total CNAs detected in non-dysplastic OPMDs (ND-OPMDs) in TNG and BM sites. (C) shows the number of total CNAs detected in dysplastic OPMDs (D-OPMDs) and OSCC TNG and BM sites. The bottom and the top of each box show the first and third quartile while the line inside the box represents the median (second quartile). Please notice that when the median is not shown, its value = 0. The tips of the whiskers represent the minimum and the maximum data value. CNAs are referred to as: total focal gains, TFG; total broad gains, TBG; total focal losses, TFL; total broad losses, TBL. Broad gains and broad losses correspond to gains or losses of more than half a chromosome arm, respectively. The boxes corresponding to the number of CNAs detected in TNG OPMDs/OSCCs are shown in white bars, whereas those of CNAs detected in BM OPMDs/OSCCs are shown in gray bars.

Mentions: To verify whether the overall genomic damage was differently distributed in the oral mucosa subsites that were taken into consideration, we measured the total number scores for focal and broad CNA gains and losses separately (see MM for details) for both TNG and BM subsites (the most frequent ones in our CGH dataset, Table 1). The analysis showed that the total number of both focal and broad CNA gains was higher in TNG compared to BM OPMDs/OSCCs (Fig 5A). A similar result was obtained when only ND-OPMDs were analyzed (Fig 5B). However, it must be pointed out that after correcting for multiple testing, only the association between TBG and TNG in OPMDs/OSCCs reached our fixed threshold (q-value = 0.079) (Fig 5A). Lastly, no differences were observed in the total CNA distribution between TNG and BM D-OPMDs/OSCCs (Fig 5C).


Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.

Castagnola P, Zoppoli G, Gandolfo S, Monticone M, Malacarne D, Cirmena G, Brown D, Aiello C, Maffei M, Marino R, Giaretti W, Pentenero M - PLoS ONE (2015)

Relationship between total CNAs and histological diagnosis in TNG and BM OPMDs/OSCCs.(A) shows the number of total CNAs detected in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) in tongue (TNG) and buccal mucosa (BM) sites; (B) shows the number of total CNAs detected in non-dysplastic OPMDs (ND-OPMDs) in TNG and BM sites. (C) shows the number of total CNAs detected in dysplastic OPMDs (D-OPMDs) and OSCC TNG and BM sites. The bottom and the top of each box show the first and third quartile while the line inside the box represents the median (second quartile). Please notice that when the median is not shown, its value = 0. The tips of the whiskers represent the minimum and the maximum data value. CNAs are referred to as: total focal gains, TFG; total broad gains, TBG; total focal losses, TFL; total broad losses, TBL. Broad gains and broad losses correspond to gains or losses of more than half a chromosome arm, respectively. The boxes corresponding to the number of CNAs detected in TNG OPMDs/OSCCs are shown in white bars, whereas those of CNAs detected in BM OPMDs/OSCCs are shown in gray bars.
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pone.0142294.g005: Relationship between total CNAs and histological diagnosis in TNG and BM OPMDs/OSCCs.(A) shows the number of total CNAs detected in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) in tongue (TNG) and buccal mucosa (BM) sites; (B) shows the number of total CNAs detected in non-dysplastic OPMDs (ND-OPMDs) in TNG and BM sites. (C) shows the number of total CNAs detected in dysplastic OPMDs (D-OPMDs) and OSCC TNG and BM sites. The bottom and the top of each box show the first and third quartile while the line inside the box represents the median (second quartile). Please notice that when the median is not shown, its value = 0. The tips of the whiskers represent the minimum and the maximum data value. CNAs are referred to as: total focal gains, TFG; total broad gains, TBG; total focal losses, TFL; total broad losses, TBL. Broad gains and broad losses correspond to gains or losses of more than half a chromosome arm, respectively. The boxes corresponding to the number of CNAs detected in TNG OPMDs/OSCCs are shown in white bars, whereas those of CNAs detected in BM OPMDs/OSCCs are shown in gray bars.
Mentions: To verify whether the overall genomic damage was differently distributed in the oral mucosa subsites that were taken into consideration, we measured the total number scores for focal and broad CNA gains and losses separately (see MM for details) for both TNG and BM subsites (the most frequent ones in our CGH dataset, Table 1). The analysis showed that the total number of both focal and broad CNA gains was higher in TNG compared to BM OPMDs/OSCCs (Fig 5A). A similar result was obtained when only ND-OPMDs were analyzed (Fig 5B). However, it must be pointed out that after correcting for multiple testing, only the association between TBG and TNG in OPMDs/OSCCs reached our fixed threshold (q-value = 0.079) (Fig 5A). Lastly, no differences were observed in the total CNA distribution between TNG and BM D-OPMDs/OSCCs (Fig 5C).

Bottom Line: Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM.Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains.Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

View Article: PubMed Central - PubMed

Affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.

ABSTRACT
Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

No MeSH data available.


Related in: MedlinePlus