Changes in abundance of oral microbiota associated with oral cancer.

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient.

Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis.

Background: Metastasis to the cervical (neck) lymph nodes is one of the most significant clinical factors responsible for death from oral squamous cell carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor is excised (neck dissection), even though the majority of patients will not benefit from the extra surgery. Two subtypes of oral SCC distinguished by the presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for metastasis - high for the 3q8pq20 subtype, harboring one or more of the aberrations and low for the non-3q8pq20 subtype, lacking these alterations.

Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution.

Breast cancers that are "triple-negative" for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution.

Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1+/- mice.

Basal cell carcinomas (BCCs) have relative genomic stability and relatively benign clinical behavior but whether these two are related causally is unknown. To investigate the effects of introducing genomic instability into murine BCCs, we have compared ionizing radiation-induced tumorigenesis in Ptch1(+/-) mice versus that in Ptch1(+/-) mice carrying mutant Blm alleles. We found that BCCs in Ptch1(+/-) Blm(tm3Brd/tm3Brd) mice had a trend toward greater genomic instability as measured by array comprehensive genomic hybridization and that these mice developed significantly more microscopic BCCs than did Ptch1(+/-) Blm(+/tm3Brd) or Ptch1(+/-) Blm(+/+) mice.

Acquired genomic aberrations associated with methotrexate resistance vary with background genomic instability.

Tumors vary widely in chromosomal level genome instability. To gain a better understanding of the underlying defects which foster specific types of aberrations, we investigated the response of cells of related genetic backgrounds to challenge with methotrexate. We studied mismatch repair deficient HCT116 cells, two derivatives also deficient in XRCC5 (HCT116 Ku86+/-) or BLM (HCT116 BLM-/-), and mismatch repair competent HCT116+chr3 cells.

FBXW7 and DNA copy number instability.

SKP1-cullin-F-box protein (SCF) type ubiquitin ligases degrade proteins controlling the G1/S transition. Deficiency for FBXW7 (also known as hCDC4), which encodes the F-box protein of the SCF type ubiquitin ligase is associated with genomic instability. Here, we investigated the association of FBXW7 deficiency with chromosomal instability in breast cancer.

Comparison of gene expression and DNA copy number changes in a murine model of lung cancer.

Activation of oncogenic Kras in murine lung leads to the development of numerous small adenomas, only some of which progress over time to overt adenocarcinoma. Thus, although Kras is the initiating oncogene, it is likely that secondary genetic events are required for progression from adenoma to adenocarcinoma. Some of these secondary events may also be important in human lung adenocarcinoma.

Therapy-induced malignant neoplasms in Nf1 mutant mice.

Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1(+/-) mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers.

Mapping segmental and sequence variations among laboratory mice using BAC array CGH.

We used arrays of 2069 BACs (1303 nonredundant autosomal clones) to map sequence variation among Mus spretus (SPRET/Ei and SPRET/Glasgow) and Mus musculus (C3H/HeJ, BALB/cJ, 129/J, DBA/2J, NIH, FVB/N, and C57BL/6) strains. We identified 80 clones representing 74 autosomal loci of copy number variation (|log(2)ratio| >/= 0.4).