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Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.

Kim SY, Jung SH, Kim MS, Baek IP, Lee SH, Kim TM, Chung YJ, Lee SH - Oncotarget (2015)

Bottom Line: We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC.Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations.Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.

ABSTRACT
Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.

No MeSH data available.


Related in: MedlinePlus

Somatic mutations and copy number alterations according to the receptor status(A) The PR-negative group harbored significantly more mutations and copy number alterations (CNAs) than the PR-positive group (p = 0.007 and p = 0.002, respectively). (B) Similar distribution of the higher mutation numbers in PR-negative group in the TCGA data (p = 1.47 × 10−17). (C) Survival analysis of PR-positive and PR-negative group in the TCGA data. PR-negative group showed worse prognosis than PR-positive group (p = 0.050).
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Figure 5: Somatic mutations and copy number alterations according to the receptor status(A) The PR-negative group harbored significantly more mutations and copy number alterations (CNAs) than the PR-positive group (p = 0.007 and p = 0.002, respectively). (B) Similar distribution of the higher mutation numbers in PR-negative group in the TCGA data (p = 1.47 × 10−17). (C) Survival analysis of PR-positive and PR-negative group in the TCGA data. PR-negative group showed worse prognosis than PR-positive group (p = 0.050).

Mentions: Finally, we queried genomic alterations with respect to clinicopathologic features (Table 1). Only progesterone receptor (PR) was significantly associated with genomic alteration profiles. PR (−) tumors were associated with a great number of somatic mutations (p = 0.007), CNAs (p = 0.002), co-occurrence of mutation/CNAs (p = 0.005) and the cancer Gene Census (p = 0.003) (Figure 5A, Table S9). This finding was in agreement with public data from TCGA, which also showed that the PR (−) group harbored more mutations and worse prognosis than the PR (+) group (Figure 5B–5C).


Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.

Kim SY, Jung SH, Kim MS, Baek IP, Lee SH, Kim TM, Chung YJ, Lee SH - Oncotarget (2015)

Somatic mutations and copy number alterations according to the receptor status(A) The PR-negative group harbored significantly more mutations and copy number alterations (CNAs) than the PR-positive group (p = 0.007 and p = 0.002, respectively). (B) Similar distribution of the higher mutation numbers in PR-negative group in the TCGA data (p = 1.47 × 10−17). (C) Survival analysis of PR-positive and PR-negative group in the TCGA data. PR-negative group showed worse prognosis than PR-positive group (p = 0.050).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480702&req=5

Figure 5: Somatic mutations and copy number alterations according to the receptor status(A) The PR-negative group harbored significantly more mutations and copy number alterations (CNAs) than the PR-positive group (p = 0.007 and p = 0.002, respectively). (B) Similar distribution of the higher mutation numbers in PR-negative group in the TCGA data (p = 1.47 × 10−17). (C) Survival analysis of PR-positive and PR-negative group in the TCGA data. PR-negative group showed worse prognosis than PR-positive group (p = 0.050).
Mentions: Finally, we queried genomic alterations with respect to clinicopathologic features (Table 1). Only progesterone receptor (PR) was significantly associated with genomic alteration profiles. PR (−) tumors were associated with a great number of somatic mutations (p = 0.007), CNAs (p = 0.002), co-occurrence of mutation/CNAs (p = 0.005) and the cancer Gene Census (p = 0.003) (Figure 5A, Table S9). This finding was in agreement with public data from TCGA, which also showed that the PR (−) group harbored more mutations and worse prognosis than the PR (+) group (Figure 5B–5C).

Bottom Line: We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC.Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations.Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.

ABSTRACT
Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.

No MeSH data available.


Related in: MedlinePlus