Kara Barnao

All Publications

• Examining the role of extrachromosomal DNA in lung cancer. Journal of the National Cancer Institute Khandekar, A., Hoang, P. H., Luebeck, J., Diaz-Gay, M., Zhao, W., McElderry, J. P., Hartman, C., Miraftab, M., Lee, O. W., Barnao, K. M., Jones, K., Hutchinson, A., Hicks, B., Bergstrom, E. N., Yang, Y., Nowak, M. A., Rothman, N., Pesatori, A. C., Consonni, D., Homer, R., Baine, M. K., Sholl, L. M., Joubert, P., Leduc, C., Travis, W. D., Yang, S., Lan, Q., Wedge, D. C., Yang, L., Chanock, S. J., Zhang, T., Alexandrov, L. B., Landi, M. T. 2026

  Abstract

  The role of extrachromosomal DNA (ecDNA) in lung cancer, particularly in subjects who never smoked (LCINS), remains unclear. Examination of over 1200 whole-genome-sequenced lung cancers identified ecDNA in 18.9% of patients. Recurrent amplification of MDM2 and other oncogenes via ecDNA possibly drives a LCINS subset. Tumors harboring ecDNA showed worse overall survival than tumors harboring other focal amplifications. A strong association with whole-genome doubling suggests most ecDNA reflects genomic instability in treatment-naive lung cancer.

  View details for DOI 10.1093/jnci/djag273

  View details for PubMedID 42554978

• Longitudinal characterization of mosaic chromosomal alterations identifies factors influencing clonal dynamics of leukocytes NATURE COMMUNICATIONS Kelly, R. L., Brown, D. W., Zhou, W., Hubbard, A. K., Young, C. D., Barnao, K. M., Klein, A., Dutta, D., Vogt, A., Liu, J., Wang, J., Huang, W., Freedman, N. D., Chanock, S. J., Albert, P. S., Machiela, M. J. 2026; 17 (1)

  Abstract

  Characterizing the variation in clonal trajectory of age-related mosaic chromosomal alterations (mCAs) in circulating leukocytes can identify etiologic factors influencing clonal expansion and hematologic malignancy risk. Here we scan whole blood-derived DNA of 56,324 participants from the Prostate, Lung, Colorectal, Ovarian Cancer Screening Study for mCAs and characterize 1746 longitudinal mCAs. Cross-sectional mCA clonal fraction only moderately correlates with clonal expansion rate, highlighting the utility of serial sampling for evaluating clonal trajectory. The strongest contributor to clonal expansion is genomic location of an mCA with participant age, smoking status, and co-occurring mCA types also modifying expansion rates. Germline susceptibility to mosaic Y or X loss is not associated with expansion rate, supporting independent mechanisms governing generation and expansion. Autosomal mCAs previously associated with hematologic malignancies have the highest rates of expansion, especially myeloid malignancy-associated mCAs, underscoring the importance of tracing mCA clonal dynamics for evaluating hematologic cancer risk.

  View details for DOI 10.1038/s41467-026-75996-5

  View details for Web of Science ID 001862145200005

  View details for PubMedID 42660912

  View details for PubMedCentralID PMC13522525

• Mosaic loss of the Y chromosome: a canary for respiratory aging? American journal of respiratory and critical care medicine Barnao, K. M., Machiela, M. J. 2026; 212 (7): 1412-1413

  View details for DOI 10.1093/ajrccm/aamag174

  View details for PubMedID 42085231

• Co-occurring clonal hematopoiesis exhibits strong selection and high leukemia risk. Nature communications Barnao, K. M., Hubbard, A. K., Chan, I. C., Zhou, W., Jakubek, Y. A., Genovese, G., Wong, W. S., Kelly, R. L., Young, C. D., Brown, D. W., Huang, W. Y., Freedman, N. D., Jones, K., Hutchinson, A., Hicks, B., Tran, D., Arnett, D., Barnes, K. C., Bis, J. C., Boerwinkle, E., Brody, J. A., Carson, A. P., Chasman, D. I., Cho, M. H., Desai, P., Doyle, M. F., Fornage, M., Guo, X., Heard-Costa, N., Irvin, M. R., Johnson, A. D., Kardia, S. L., Kooperberg, C., Levy, D., Lewis, J. P., Li, Y., Loos, R. J., Mack, T. M., Mathias, R. A., Mitchell, B. D., North, K. E., Pankratz, N., Peyser, P. A., Preuss, M. H., Psaty, B. M., Raffield, L. M., Redline, S., Rich, S. S., Rotter, J. I., Silverman, E. K., Smith, A. V., Smith, J. A., Stilp, A., Cao, Y., Scheet, P., Reiner, A. P., Bick, A. G., Chanock, S. J., Auer, P. L., Bolton, K. L., Machiela, M. J. 2026; 17 (1)

  Abstract

  Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have pronounced elevations in risk of myeloid and lymphoid malignancies (HRs>40), particularly when CHIP and mCAs overlap genomically. Our findings indicate CH co-occurrences are selected for in the aging population and identify CH clones with notable implications for future malignancy risk.

  View details for DOI 10.1038/s41467-026-73302-x

  View details for PubMedID 42168198

  View details for PubMedCentralID PMC13385913