BACKGROUND: Aberrations in DNA methylation patterns are well-described in human malignancies. However, the existence of the 'CpG island methylator phenotype' (CIMP) in human breast cancer is still controversial. MATERIALS & METHODS: Illumina's HumanMethylation 450K BeadChip was used to analyze genome-wide DNA methylation patterns. Chromosomal abnormalities were determined by array-based CGH. RESULTS: Invasive lobular breast carcinomas exhibit the highest number of differentially methylated CpG sites and a strong inverse correlation of aberrant DNA hypermethylation and copy number alterations. Nine differentially methylated regions within seven genes discriminating the investigated subgroups were identified and validated in an independent validation cohort and correlated to a better relapse-free survival. CONCLUSION: These results depict a clear difference between genetically and epigenetically unstable breast carcinomas indicating different ways of tumor progression and/or initiation, which strongly supports the association of CIMP with the lobular subtype and provide new options for detection and therapy.
BACKGROUND: Aberrations in DNA methylation patterns are well-described in humanmalignancies. However, the existence of the 'CpG island methylator phenotype' (CIMP) in humanbreast cancer is still controversial. MATERIALS & METHODS: Illumina's HumanMethylation 450K BeadChip was used to analyze genome-wide DNA methylation patterns. Chromosomal abnormalities were determined by array-based CGH. RESULTS: Invasive lobular breast carcinomas exhibit the highest number of differentially methylated CpG sites and a strong inverse correlation of aberrant DNA hypermethylation and copy number alterations. Nine differentially methylated regions within seven genes discriminating the investigated subgroups were identified and validated in an independent validation cohort and correlated to a better relapse-free survival. CONCLUSION: These results depict a clear difference between genetically and epigenetically unstable breast carcinomas indicating different ways of tumor progression and/or initiation, which strongly supports the association of CIMP with the lobular subtype and provide new options for detection and therapy.
Entities:
Keywords:
CpG island methylator phenotype; DNA methylation; breast cancer; epigenetics; lobular breast cancer
Authors: Belén Pérez-Mies; Tamara Caniego-Casas; Irene Carretero-Barrio; Michele Biscuola; María A López-García; David Hardisson; Marta Rosas; María J López Rodríguez; Eva Cristóbal; David Pizarro; Juan M Rosa-Rosa; José Palacios Journal: Am J Surg Pathol Date: 2022-07-25 Impact factor: 6.298
Authors: Sara Ahmed Aglan; Ahmad Mohamad Zaki; Amel Sobhy El Sedfy; Heba Gaber El-Sheredy; Ola Hussein Elgaddar Journal: Rep Biochem Mol Biol Date: 2022-04
Authors: Sara Hetzel; Alexandra L Mattei; Helene Kretzmer; Chunxu Qu; Xiang Chen; Yiping Fan; Gang Wu; Kathryn G Roberts; Selina Luger; Mark Litzow; Jacob Rowe; Elisabeth Paietta; Wendy Stock; Elaine R Mardis; Richard K Wilson; James R Downing; Charles G Mullighan; Alexander Meissner Journal: Nat Cancer Date: 2022-05-19