Publications

Current Preprints

Graham MK, Xu B, Davis C, Meeker AK, Heaphy CM, Yegnasubramanian S, Dyer MA, Zeineldin M. The TERT promoter is polycomb-repressed in neuroblastoma cells with long telomeres. bioRxiv 2022;https://doi.org/10.1101/2022.05.18.492493.

Jafari N, Kolla M, Pompa IR, Qiu Y, Ennis CS, Mori J, Mahdaviani K, Halpin M, Gignac GA, Heaphy CM, Denis GV. Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease. bioRxiv 2022;https://doi.org/10.1101/2022.02.01.478722.

2022

Heaphy CM, Singhi AD. The Diagnostic and Prognostic Utility of Incorporating DAXX, ATRX, and Alternative Lengthening of Telomeres (ALT) to the Evaluation of Pancreatic Neuroendocrine Tumors (PanNETs). Human Pathology 2022 Jul 21:S0046-8177(22)00189-7. (Invited Review)

Heaphy CM, Joshu CE, Barber JR, Davis C,Lu J, Zarinshenas R, Giovannucci E, Mucci LA, Stampfer MJ, Han M, De Marzo AM, Lotan TL, Platz EA, Meeker AK. The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy. Journal of Pathology: Clinical Research 2022 Jul 14. doi: 10.1002/cjp2.288.

Yuan M, Eberhart CG, Pratilas CA, Blakeley J, Davis C, Stojanova M, Reilly K, Meeker AK, Heaphy CM, Rodriguez FJ. Therapeutic vulnerability to ATR inhibition in concurrent NF1 and ATRX-deficient high-grade solid tumors. Cancers 2022;14:3015.

Mori JO, Shafran JS, Stojanova M, Katz MH, Gignac GA, Wisco JJ, Heaphy CM, Denis GV. Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins. The Prostate 2022;82:1005-15. (Review)

Lally SE, Milman T, Dalvin LA, Orloff M, Eberhart CG, Heaphy CM, Rodriguez FJ, Lin CC, Dockery PW, Shields JA, Shields CL. Mutational landscape and outcomes of conjunctival melanoma in 101 patients. Ophthalmology 2022;129:679-93.

Dreijerink KMA, Hackeng WM, Singhi AD, Heaphy CM, Brosens LAA. Clinical implications of cell-of-origin epigenetic characteristics in non-functional pancreatic neuroendocrine tumors. Journal of Pathology 2022;256:143-8. (Invited Review)

Hackeng WM, Brosens LAA, Kim JY, O’Sullivan RJ, Sung Y, Liu T, Cao D, Heayn M, Brosnan-Cashman JA, An D, Morsink FHM, Heidsma CM, Valk GD, Vriens MR, Nieveen van Dijkum EJM, Offerhaus GJA, Dreijerink KMA, Zeh HJ, Zureikat AH, Hogg ME, Lee K, Geller D, Marsh JW, Paniccia A, Ongchin MC, Pingpank JF, Bahary N, Aijazi M, Brand RE, Chennat JS, Das R, Fasanella KE, Khalid A, McGrath K, Sarkaria S, Singh H, Slivka A, Nalesnik MA, Han X, Nikiforova MN, Lawlor RT, Mafficini A, Rusev B, Corbo V, Luchini C, Bersani S, Pea A, Cingarlini S, Landoni L, Salvia R, Milione M, Milella M, Scarpa A, Hong SM, Heaphy CM, Singhi AD. Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size. Gut 2022;71:961-73. (Accompanying Editorial)

Heaphy CM, Zarinshenas R, Barber JR, Davis C, Brosnan-Cashman JA, De Marzo AM, Joshu CE, Platz EA, Meeker AK. A high-throughput approach measures cell type-specific telomere lengths in fixed archival tissues from patient cohorts for research on prognosis. medRxiv 2022 https://doi. org/10.1101/2022.01.20.22269597.

2021

Shrestha E, Coulter JB, Guzman W, Ozbek B, Hess MM, Mummert L, Ernst SE, Maynard JP, Meeker AK, Heaphy CM, Haffner MC, De Marzo AM, Sfanos KS. Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer. Proceedings of the National Academy of Science (PNAS) USA 2021;118:e2018976118.

Heaphy CM, VandenBussche CJ. Prognostic biomarkers in pancreatic neuroendocrine tumors. Cancer Cytopathology 2021;129:841-3. (Molecular Minute)

Brosnan-Cashman JA, Davis CM, Diplas BH, Meeker AK, Rodriguez FJ, Heaphy CM. SMARCAL1 loss and alternative lengthening of telomeres (ALT) are enriched in giant cell glioblastoma. Modern Pathology 2021; 34:1810-9.

Kang HJ, Oh JH, Kim YW, Kim W, An J, Sung CO, Kim J, Shim JH, Hwang S, Yu E, Heaphy CM, Hong SM. Clinicopathological and molecular characterization of chromophobe hepatocellular carcinoma. Liver International 2021;41:2499-510.

Sullivan HH, Maynard JP, Heaphy CM, Lu J, De Marzo AM, Lotan TL, Joshu CE, Sfanos KS. Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes. Journal of Pathology 2021;253:415-26.

Joshu CE, Heaphy CM, Barber JR, Lu J, Zarinshenas R, Davis C, Han M, Lotan TL, Sfanos KS, De Marzo AM, Meeker AK, Platz EA. Obesity is associated with shorter telomere length in prostate stromal cells in men with aggressive prostate cancer. Cancer Prevention Research 2021;14:463-70.

Meeker AK, Heaphy CM, Davis CM, Roy S, Platz EA. Photochemical pre-bleaching of formalin-fixed archival prostate tissues significantly reduces autofluorescence to facilitate multiplex immunofluorescence staining. bioRxiv 2021;https://doi.org/10.1101/2021.11.09.467916.

2020

Esopi D, Graham MK, Brosnan-Cashman JA, Meyers J, Vaghasia A, Gupta A, Kumar B, Haffner MC,Heaphy CM, De Marzo AM, Meeker AK, Nelson WG, Wheelan SJ, Yegnasubramanian S. Pervasive promoter hypermethylation of silenced TERT alleles in human cancers. Cellular Oncology 2020;43:847-61.

Heaphy CM, Haffner MC, Graham MK, Lim D, Davis C, Corey E, Epstein JI, Eisenberger MA, Wang H, De Marzo AM, Meeker AK, Lotan TL. Telomere lengths differ significantly between small cell neuroendocrine prostate carcinoma and adenocarcinoma of the prostate. Human Pathology 2020;101:70-9.

Heaphy CM, Bi WL, Coy S, Davis C, Gallia GL, Santagata S, Rodriguez FJ. Telomere length alterations and ATRX/DAXX loss in pituitary adenomas. Modern Pathology 2020;33:1475-81.

Hackeng WM, Schelhaas W, Morsink FHM, Heidsma CM, van Eeden S, Valk GD, Vriens MR, Heaphy CM, Nieveen van Dijkum EJM, Offerhaus GJA, Dreijerink KMA, Brosens LAA. Alternative Lengthening of Telomeres and differential expression of endocrine transcription factors distinguish metastatic and non-metastatic insulinomas. Endocrine Pathology 2020:31:108-18.

Kim JK, Brosnan-Cashman JA, Kim J, An S, Lee KB, Kim H, Park DY, Jang KT, Oh YH, Hruban RH, Heaphy CM, Hong SM. Pancreatic acinar cell carcinomas and mixed acinar-neuroendocrine carcinomas are more clinically aggressive than grade 1 pancreatic neuroendocrine tumor. Pathology 2020;52:336-47.

Pieterman CRC, Sadowski SM, Maxwell JE, Katz MHG, Lines KE, Heaphy CM, Tirosh A, Blau JE, Perrier ND, Lewis MA, Metzcar JP, Halperin DM, Thakker RV, Valk GD. MEN1-related pancreatic NETs: Identification of unmet clinical needs and future directives. Endocrine-Related Cancer 2020;27:9-25. (World MEN 2019 Pancreatic NET Working Group)

Felsenstein M, Trujillo MA, Huang B, Nanda N, Jiang Z, Jeong YJ, Pflüger M, Goggins MG, Hruban RH, Thompson ED, Heaphy CM, Roberts NJ, Wood LD. Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas. Laboratory Investigation 2020;100:1003-13.

Sullivan HH, Heaphy CM, Kulac I, Cuka NS, Lu J, Barber JR, De Marzo AM, Lotan TL, Joshu CE, Sfanos KS. High extra-tumoral mast cell counts are associated with a higher risk of adverse prostate cancer outcomes. Cancer Epidemiology, Biomarkers & Prevention 2020;29:668-75.

Heaphy CM, Joshu CE, Barber JR, Davis C, Zarinshenas R, De Marzo AM, Lotan TL, Sfanos KS, Meeker AK, Platz EA. Racial difference in prostate cancer cell telomere lengths in men with higher-grade prostate cancer: a clue to the racial disparity in prostate cancer outcomes. Cancer Epidemiology, Biomarkers & Prevention 2020;29:676-80.

Hackeng WM, Morsink FH, Moons LMG, Heaphy CM, Offerhaus GJA, Dreijerink KMA, Brosens LAA. Assessment of ARX expression, a novel biomarker for metastatic risk in pancreatic neuroendocrine tumors, in endoscopic ultrasound fine needle aspiration. Diagnostic Cytopathology 2020;48:308-15.

Pea A, Yu J, Marchionni L, Noe M, Luchini C, Pulvirenti A, de Wilde RF, Brosens LA, Rezaee N, Javed A, Gobbo S, Regi P, Salvia R, Bassi C, He J, Weiss MJ, Cameron JL, Offerhaus GJA, Hruban RH, Lawlor RT, Scarpa A, Heaphy CM, Wood LD, Wolfgang CL. Genetic analysis of small well-differentiated pancreatic neuroendocrine tumors identifies subgroups with differing risks of liver metastases. Annals of Surgery 2020;271:566-73. (Accompanying Editorial)

 

2019

Graham M.K., Kim J., Da J., Brosnan-Cashman J.A., Rizzo A., Baena Del Valle J.A., Chia L., Rubenstein M., Davis C., Zheng Q., Cope L., Considine M., Haffner M.C., De Marzo A.M., Meeker A.K., Heaphy C.M. Functional loss of ATRX and TERC activates Alternative Lengthening of Telomeres (ALT) in LAPC4 prostate cancer cells. Molecular Cancer Research 2019;17:2480-91.

Tomasetti C., Poling J., Roberts N.J., London Jr N.R., Pittman M.E., Haffner M.C., Rizzo A., Baras A., Karim B., Kim A., Heaphy C.M., Meeker A.K., Hruban R.H., Iacobuzio-Donahue C.A., Vogelstein B. Stem cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence. Proceedings of the National Academy of Science (PNAS) USA 2019;116:20482-8. (Press Release)

Cejas P., Drier Y., Dreijerink K.M.A., Brosens L.A.A., Deshpande V., Epstein C.B., Conemans E.B., Morsink F.H.M., Graham M.K., Valk G.D., Vriens M.R., Fernandez-del Castillo C., Ferrone C., Adar T., Bowden M., Whitton H., Da Silva A., Font-Tello A., Long H.W., Gaskell E., Shoresh N., Heaphy C.M., Sicinska E., Kulke M.H., Chung D.C., Bernstein B.E., Shivdasani R.A. Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumours. Nature Medicine 2019;25:1264-9. (Press Release) (Reviewed by Endocrine Surgery)

Flynn R.L., Heaphy C.M. Surviving telomere attrition with the MiDAS touch. Trends in Genetics 2019;35:783-5. (Invited Commentary on Min et al.)

Rodriguez F.J., Graham M.K., Brosnan-Cashman J.A., Barber J.R., Davis C., Vizcaino M.A., Palsgrove D.N., Giannini C., Pekmezci M., Dahiya S., Gokden M., Noë M., Wood L.D., Pratilas C.A., Morris C., Belzberg A., Blakeley J., Heaphy C.M. Telomere alterations in neurofibromatosis type 1-associated solid tumors. Acta Neuropathologica Communications 2019;7:139. (Press Release)

Zarif J.C., Baena-Del Valle J.A., Hicks J.L., Heaphy C.M., Vidal I., Luo J., Lotan T.L., Hooper J.E., Isaacs W.B., Pienta K.J., De Marzo A.M. Mannose Receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castrate-resistant disease. European Urology Oncology 2019;2:429-36.

Martínez H., Nagurney M., Wang Z.X., Eberhart C.G., Heaphy C.M., Curtis M.T., Rodriguez F.J. ATRX mutations in pineal parenchymal tumors of intermediate differentiation. Journal of Neuropathology & Experimental Neurology 2019;78:703-8.

Asaka S., Davis C., Lin S.F., Wang T.L., Heaphy C.M., Shih I.M. Analysis of telomere lengths in p53 signatures and incidental serous tubal intraepithelial carcinomas without cancer. American Journal of Surgical Pathology 2019;43:1083-91.

Trabzonlu L., Kulac I., Zheng Q., Hicks J.L., Haffner M.C., Nelson W.G., Sfanos K.S., Ertunc O., Lotan T.L., Heaphy C.M., Meeker A.K., Yegnasubramanian S., De Marzo A.M. Molecular Pathology of High-Grade Prostatic Intraepithelial Neoplasia: Challenges and Opportunities. Cold Spring Harbor Perspective in Medicine 2019;9:a030403. (Invited Review)

Rodriguez F.J., Brosnan-Cashman J.A., Allen S.J., Vizcaino M.A., Giannini C., Camelo-Piragua S., Webb M., Matsushita M., Wadhwani N., Tabbarah A., Hamideh D., Jiang L., Chen L., Arvantis L., Alnajar H.H., Barber J.R., Rodriguez-Velasco A., Orr B., Heaphy C.M. Alternative Lengthening of Telomeres, ATRX loss and H3 p.K27M mutations in histologically defined anaplastic pilocytic astrocytoma. Brain Pathology 2019;29:126-40.

Bell W.R., Meeker A.K., Rizzo A., Rajpara S., Rosenthal I.M., Flores Bellver M., Aparicio Domingo S., Zhong X., Barber J.R., Joshu C.E., Canto-Soler M.V., Eberhart C.G., Heaphy C.M. A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. Brain Pathology 2019;29:45-52. (Journal Cover)

Marrone M.T., Joshu C.E., Peskoe S.B., De Marzo A.M., Heaphy C.M., Lupold S.E., Meeker A.K., Platz E.A. Adding the team into T1 translational research: a case study of multidisciplinary team science in the evaluation of biomarkers of prostate cancer risk and prognosis. Clinical Chemistry 2019;65:189-98.

 

Selected Publications (2011-2018)

Brosnan-Cashman J.A., Yuan M., Graham M.K., Rizzo A.J., Myers K., Davis C., Zhang R., Esopi D.M., Raabe E.H., Eberhart C.G., Heaphy C.M., Meeker A.K. ATRX loss induces multiple hallmarks of the alternative lengthening of telomeres (ALT) phenotype in human glioma cell lines in a cell line-specific manner. PLoS ONE 2018;13:e0204159.

Baena Del Valle J.A., Zheng Q., Esopi D.M., Rubenstein M., Hubbard G.K., Moncaliano M.C., Hruszkewycz A., Vaghasia A., Yegnasubramanian S., Wheelan S.J., Meeker A.K., Heaphy C.M., Graham M.K., De Marzo A.M. MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer. Journal of Pathology 2018;244:11-24.

Brosnan-Cashman J.A., Graham M.K., Heaphy C.M. Genetic alterations associated with ALTered telomeres. Oncotarget 2018;9:33739-40. (Invited Commentary on Mason-Osann et al.)

Palsgrove D., Brosnan-Cashman J.A., Giannini C., Raghunathan A., Jentoft M., Bettegowda C., Gokden M., Ho C.Y., Lin M.T., Heaphy C.M., Rodriguez F.J. Subependymal giant cell astrocytoma -like astrocytoma: a neoplasm with a distinct phenotype and frequent neurofibromatosis type 1-association. Modern Pathology 2018;31:1787-1800.

Kim J.Y., Brosnan-Cashman J.A., An S., Kim S.J., Song K.B., Kim M.S., Kim M.J., Hwang D.W., Meeker A.K., Yu E., Kim S.C., Hruban R.H., Heaphy C.M., Hong S.M.. Alternative lengthening of telomeres in primary pancreatic neuroendocrine neoplasms is associated with aggressive clinical behavior and poor survival. Clinical Cancer Research 2017;23:1598-606.

VandenBussche J., Allison D.B., Graham M.K., Charu V., Lennon A.M., Wolfgang C.L., Hruban R.H., Heaphy C.M. Alternative lengthening of telomeres and ATRX/DAXX loss can reliably be detected in fine needle aspirates of pancreatic neuroendocrine tumors. Cancer Cytopathology 2017;125:544-51.

Rodriguez F.J., Vizcaino M.A., Blakeley J., Heaphy C.M. Frequent Alternative Lengthening of Telomeres and ATRX loss in adult NF1-associated diffuse and high grade astrocytomas. Acta Neuropathologica 2016;132:761-3.

Heaphy C.M., Gaonkar G., Peskoe S.B., Joshu C.E., De Marzo A.M., Lucia M.S., Goodman P.J., Lippman S.M., Thompson I.M., Platz E.A., Meeker A.K. Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial. The Prostate 2015;75:1160-6.

Meeker AK, Heaphy CM. Gastroenteropancreatic endocrine tumors. Molecular and Cellular Endocrinology 2014;386:101-20. (Invited Review)

Dogeas E, Karagkounis G, Heaphy CM, Hirose K, Pawlik TM, Wolfgang CL, Meeker AK, Hruban RH, Cameron JL, Choti MA. Alternative lengthening of telomeres predicts site of origin in neuroendocrine tumor liver metastases. Journal of the American College of Surgeons 2014;218:628-35. (Accompanying Discussion)

Haffner M.C., Mosbruger T., Esopi D.M., Fedor H., Heaphy C.M., Walker D.A., Adejola N., Gurel M., Hicks J., Meeker A.K., Halushka M.K., Simons J.W., Isaacs W.B., De Marzo A.M., Nelson W.G., Yegnasubramanian S. Tracking the clonal origin of lethal prostate cancer. Journal of Clinical Investigation 2013;123:4918-22. (Accompanying Editorial) (Highlighted in European Urology) (Highlighted in Nature Reviews Clinical Oncology)

Heaphy C.M., Yoon G.S., Peskoe S.B., Joshu C.E., Lee T.K., Giovannucci E., Mucci L.A., Kenfield S.A., Stampfer M.J., Hicks J.L., De Marzo A.M., Platz E.A., Meeker A.K. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discovery 2013;3:1130-41. (Press Release) (Accompanying Editorial)

Heaphy C.M., Schreck K.C., Raabe E., Mao X., Chu Q., An P., Poh W., Jiao Y., Rodriguez F.J., Odia Y., Meeker A.K., Eberhart C.G. A glioblastoma neurosphere line with alternative lengthening of telomeres. Acta Neuropathologica 2013;126:607-8.

Jiao Y., Killela P.J., Reitman Z.J., Rasheed B.A., Heaphy C.M., de Wilde R.F., Rodriguez F.J., Rosemberg S, Obashinjo S.M., Nagahashi Marie S.K., Bettegowda C., Agrawal N., Lipp E., Pirozzi C., Lopez G., He Y., Friedman H., Friedman A.H., Riggins G.J., Holdhoff M., Burger P., McLendon R., Bigner D.D., Vogelstein B., Meeker A.K., Kinzler K.W., Papadopoulos N., Diaz Jr. L.A., Yan H. Frequent ATRX, CIC, and FUBP1 mutations refine the classification of malignant gliomas. Oncotarget 2012;3:709-22.

Heaphy CM, Meeker AK. The potential utility of telomere-related markers for cancer diagnosis. Journal of Cellular and Molecular Medicine 2011;15:1227-38. (Review)

Konishi H., Mohseni M., Tamaki A., Garay J.P., Croessmann S., Karnan S., Ota A., Wong H.Y., Konishi Y., Karakas B., Tahir K., Abukhdeir A.M., Gustin J.P., Cidado J., Wang G.M., Cosgrove D., Cochran R., Jelovac D., Higgins M.J., Arena S., Hawkins L., Lauring J., Gross A.L., Heaphy C.M., Hosokawa Y., Gabrielson E., Meeker A.K., Visvanathan K., Argani P., Bachman K.E., Park B.H. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proceedings of the National Academy of Science (PNAS) USA 2011;108:17773-8. (Highlighted in Women’s Health)

Heaphy C.M., Subhawong A.P., Hong S.M., Goggins M.G., Montgomery E.A., Gabrielson E., Netto G.J., Epstein J.I., Lotan T.L., Westra W.H., Shih I.M., Iacobuzio-Donahue C.A., Maitra A., Li Q.K., Eberhart C.G., Taube J.M., Rakheja D., Kurman R.J., Wu T., Roden R.B., Argani P., De Marzo A.M., Terracciano L., Torbenson M., Meeker A.K. Prevalence of the Alternative Lengthening of Telomeres (ALT) telomere maintenance mechanism in human cancer subtypes. The American Journal of Pathology 2011;179:1608-15. (Press Release)

Wang Y., Meeker A.K., Kowalski J., Tsai H.L., Somervell H., Heaphy C.M., Sangenario L.E., Prasad N., Westra W.H., Zeiger M.A., Umbricht C.B. Telomere length is related to alternative splice patterns of telomerase in thyroid tumors. The American Journal of Pathology 2011;179:1415-24.

Heaphy C.M., de Wilde R.F., Jiao Y., Klein A.P., Edil B.H., Shi C., Bettegowda C., Rodriguez F.J., Eberhart C.G., Hebbar S., Offerhaus G.J., McLendon R., Rasheed B.A., He Y., Yan H., Bigner D.D., Oba-Shinjo S.M., Nagahashi Marie S.K., Riggins G.J., Kinzler K.W., Vogelstein B., Hruban R.H., Maitra A., Papadopoulos N., Meeker A.K. Altered telomeres in tumors with ATRX and DAXX. Science 2011;333:425. (Press Release) (Highlighted in JAMA)