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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.


Related in: MedlinePlus

Relationship between total CNAs and histological diagnosis in OPMDs/OSCCs.The bottom and the top of each box show the first and third quartile, respectively, 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. Oral potentially malignant disorders (OPMDs); oral squamous cell carcinomas (OSCCs); non-dysplastic oral potentially malignant disorders (ND-OPMDs); dysplastic oral potentially malignant disorders (D-OPMDs). 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 ND-OPMD sites are shown in white; the boxes corresponding to the number of CNAs detected in mucosa sites affected by D-OPMDs and OSCCs are shown in gray. Significant MW P-values (P < 0.05) and their corresponding q-values are shown. The FDR q-value method was applied for multiple testing (n = 4) correction; q-values < 0.1 are indicated in bold. N = 94 OPMDs/OSCCs; N = 46 ND-OPMDs; N = 48 D-OPMDs/OSCCs.
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pone.0142294.g003: Relationship between total CNAs and histological diagnosis in OPMDs/OSCCs.The bottom and the top of each box show the first and third quartile, respectively, 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. Oral potentially malignant disorders (OPMDs); oral squamous cell carcinomas (OSCCs); non-dysplastic oral potentially malignant disorders (ND-OPMDs); dysplastic oral potentially malignant disorders (D-OPMDs). 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 ND-OPMD sites are shown in white; the boxes corresponding to the number of CNAs detected in mucosa sites affected by D-OPMDs and OSCCs are shown in gray. Significant MW P-values (P < 0.05) and their corresponding q-values are shown. The FDR q-value method was applied for multiple testing (n = 4) correction; q-values < 0.1 are indicated in bold. N = 94 OPMDs/OSCCs; N = 46 ND-OPMDs; N = 48 D-OPMDs/OSCCs.

Mentions: To determine whether the total DNA damage in terms of CNAs was differently distributed between the two histology groups (ND-OPMD versus D-OPMD/OSCC), the CNA data identified by the GISTIC analysis were processed as described in the Materials and Methods section, and the TFG, TBG, TFL and TBL were calculated for each histology group (Fig 3). Statistical analysis performed with the non-parametric MW two-tailed test showed that TBG, TFL and TBL were significantly higher in the D-OPMDs/OSCCs (P = 3.3E-02, P = 2.9E-02 and P = 4.6E-03, respectively; 95% CI) (Fig 3).


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 OPMDs/OSCCs.The bottom and the top of each box show the first and third quartile, respectively, 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. Oral potentially malignant disorders (OPMDs); oral squamous cell carcinomas (OSCCs); non-dysplastic oral potentially malignant disorders (ND-OPMDs); dysplastic oral potentially malignant disorders (D-OPMDs). 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 ND-OPMD sites are shown in white; the boxes corresponding to the number of CNAs detected in mucosa sites affected by D-OPMDs and OSCCs are shown in gray. Significant MW P-values (P < 0.05) and their corresponding q-values are shown. The FDR q-value method was applied for multiple testing (n = 4) correction; q-values < 0.1 are indicated in bold. N = 94 OPMDs/OSCCs; N = 46 ND-OPMDs; N = 48 D-OPMDs/OSCCs.
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pone.0142294.g003: Relationship between total CNAs and histological diagnosis in OPMDs/OSCCs.The bottom and the top of each box show the first and third quartile, respectively, 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. Oral potentially malignant disorders (OPMDs); oral squamous cell carcinomas (OSCCs); non-dysplastic oral potentially malignant disorders (ND-OPMDs); dysplastic oral potentially malignant disorders (D-OPMDs). 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 ND-OPMD sites are shown in white; the boxes corresponding to the number of CNAs detected in mucosa sites affected by D-OPMDs and OSCCs are shown in gray. Significant MW P-values (P < 0.05) and their corresponding q-values are shown. The FDR q-value method was applied for multiple testing (n = 4) correction; q-values < 0.1 are indicated in bold. N = 94 OPMDs/OSCCs; N = 46 ND-OPMDs; N = 48 D-OPMDs/OSCCs.
Mentions: To determine whether the total DNA damage in terms of CNAs was differently distributed between the two histology groups (ND-OPMD versus D-OPMD/OSCC), the CNA data identified by the GISTIC analysis were processed as described in the Materials and Methods section, and the TFG, TBG, TFL and TBL were calculated for each histology group (Fig 3). Statistical analysis performed with the non-parametric MW two-tailed test showed that TBG, TFL and TBL were significantly higher in the D-OPMDs/OSCCs (P = 3.3E-02, P = 2.9E-02 and P = 4.6E-03, respectively; 95% CI) (Fig 3).

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