title: Family with acute myelocytic leukemia, breast, ovarian, and gastrointestinal cancer.
abstract: We report a multigeneration family in which hematologic cancers, particularly acute myelocytic leukemia (AML), and solid tumors were interspersed in cancer-prone lineages consistent with an autosomal dominant mode of genetic transmission. This combination of AML and solid tumors, in the absence of a known hereditary disorder such as the Li-Fraumeni syndrome, appears to be unique. This pedigree appears to support our hypothesis of a genetic susceptibility to both solid tumors and hematologic cancer in this kindred. Our study involved the genetic work-up of the family and the education of high-risk patients. Medical and pathology reports were retrieved for cross-referencing and verification of family reports. Blood collected through venipuncture and, when available, diagnostic bone marrow specimens were obtained for cytogenetic studies, inclusive of multiflour fluorescence in situ hybridization (M-FISH) and G-banding methods. Slides and tissue blocks were reviewed, when available. No constitutional chromosomal abnormality or rearrangement and no abnormal platelet count or function was identified in cancer-affected members or high-risk relatives in this family. However, two family members affected with AML exhibited abnormal acquired clones in their bone marrow specimens by both G-band studies and interphase FISH, both with a deletion of 5q.
authors.affiliation: Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA. htlynch@creighton.edu
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Brigid
authors.initials: B
authors.lastname: Quinn-Laquer
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Snyder
authors.forename: Jane F
authors.initials: JF
authors.lastname: Lynch
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lipkin
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree