title: Mutant allele specific imbalance in oncogenes with copy number alterations: Occurrence, mechanisms, and potential clinical implications.
abstract: Mutant allele specific imbalance (MASI) was initially coined to describe copy number alterations associated with the mutant allele of an oncogene. The copy number gain (CNG) specific to the mutant allele can be readily observed in electropherograms. With the development of genome-wide analyses at base-pair resolution with copy number counts, we can now further differentiate MASI into those with CNG, with copy neutral alteration (also termed acquired uniparental disomy; UPD), or with loss of heterozygosity (LOH) due to the loss of the wild-type (WT) allele. Here we summarize the occurrence of MASI with CNG, aUPD, or MASI with LOH in some major oncogenes (such as EGFR, KRAS, PIK3CA, and BRAF). We also discuss how these various classifications of MASI have been demonstrated to impact tumorigenesis, progression, metastasis, prognosis, and potentially therapeutic responses in cancer, notably in lung, colorectal, and pancreatic cancers.
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
authors.forename: Wanglong
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Juang
authors.affiliation: Department of Pathology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Mansukhani
authors.affiliation: Department of Oncology, Montefiore/Albert Einstein Cancer Center, Bronx, NY, USA.
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA; Department of Pathology, Columbia University Medical Center, New York, NY, USA; Department of Otolaryngology and Head and Neck Cancer, Columbia University Medical Center, New York, NY, USA. Electronic address: gs2157@columbia.edu.
authors.forename: Gloria H
authors.initials: GH
authors.lastname: Su
mesh_terms: D022981:Allelic Imbalance; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000235:genetics; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D024182:Uniparental Disomy
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: EGFR; KRAS; Loss of wild-type allele; MASI; PDAC; UPD