{
  "abstract": "Aims A subset of microglandular adenosis (MGA) displays protein expression and molecular genetic alterations similar to those of synchronous triple-negative breast carcinoma (TNBC), supporting the hypothesis that MGA is a non-obligate precursor lesion to a subset of breast carcinomas. Here, we further explore this association in the context of genomic instability.Methods We use whole-genome sequencing to investigate the genetic landscape of two unusual cases of MGA associated with carcinoma in the setting of two distinct varieties of genomic instability.Results The first case describes a patient with Lynch Syndrome developing a low-grade TNBC of the left breast with adenoid cystic-like and MGA-like growth patterns and a contralateral, right breast MGA. Both carcinoma and contralateral MGA showed loss of MSH2 and MSH6 proteins. Molecular studies identified somatic TP53 hotspot mutation only in carcinoma. A germline MSH2 mutation was detected in all samples, and somatic MSH2 pathogenic mutation was detected only in carcinoma components, while the contralateral MGA displayed loss-of-heterozygosity of the wild-type allele, indicating distinct mechanisms of biallelic inactivation of MSH2 between the samples. The second case consists of atypical MGA and associated high-grade TNBC arising in a setting of homologous recombination deficiency (HRD) with molecular signatures suggestive of BRCA2-like/HRD-associated mutational features in addition to shared TP53 alterations.Conclusions Genomic instability, either due to mismatch repair protein deficiency or due to HRD, may play a role in MGA, MGA-associated carcinogenesis and distinct morphological patterns.",
  "authors": [
    {
      "affiliations": [
        "Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Mariel Bedell"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Edaise M da Silva"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Pier Selenica"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Andrea M Gazzo"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Juan Blanco Heredia"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Thais Basili"
    },
    {
      "affiliations": [
        "Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Esther Elishaev"
    },
    {
      "affiliations": [
        "Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Lakshmi Harinath"
    },
    {
      "affiliations": [
        "Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Emilia Diego"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Nishant Tageja"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Britta Weigelt"
    },
    {
      "affiliations": [
        "Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Jorge S Reis-Filho"
    },
    {
      "affiliations": [
        "Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Rohit Bhargava"
    }
  ],
  "title": "Microglandular adenosis, triple negative breast carcinoma and DNA repair defects",
  "uid": "25192847-3324-58da-9a58-47f4669fd777"
}