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Molecular Determinants of Radiosensi...

Ahmed, Mona.

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Molecular Determinants of Radiosensitivity in Merkel Cell Carcinoma.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Molecular Determinants of Radiosensitivity in Merkel Cell Carcinoma./
作者:	Ahmed, Mona.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2022,
面頁冊數:	144 p.
附註:	Source: Dissertations Abstracts International, Volume: 84-05, Section: B.
Contained By:	Dissertations Abstracts International84-05B.
標題:	Virology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29390789
ISBN:	9798357575753

Molecular Determinants of Radiosensitivity in Merkel Cell Carcinoma.
Ahmed, Mona.

Molecular Determinants of Radiosensitivity in Merkel Cell Carcinoma. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 144 p.

Source: Dissertations Abstracts International, Volume: 84-05, Section: B.

Thesis (Ph.D.)--Harvard University, 2022.

This item must not be sold to any third party vendors.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two etiologies. Polyomavirus-associated MCC (MCCP) is caused by clonal integration of Merkel cell polyomavirus into host DNA. MCCP tumors typically have few mutations and often contain wild type (WT) p53. Nonviral MCC (MCCN) is caused by excessive exposure to ultraviolet radiation from sunlight and frequently harbors mutations in the p53 tumor suppressor. Despite their distinct etiologies, MCCP and MCCN tumors have similar histologic and clinical features and treatment strategies. For example, localized MCC is typically managed by surgical excision of the primary tumor and draining lymph nodes, followed by adjuvant radiation therapy. Inoperable tumors are treated with radiation therapy alone, as MCC is a highly radiosensitive cancer. Radiation therapy alone leads to similar survival rates as observed inpatients treated with surgery. Despite these similarities, MCCN behaves more aggressively than MCCP with an increased risk of disease progression, recurrence, and death. Viral status is not routinely considered when deciding on a course of treatment and it is not known if there are intrinsic differences in MCCP and MCCN radiosensitivity. To test this, we characterized the response to radiation in MCC cell lines with different viral and p53 statuses. We observed that loss of p53 function rendered MCC resistant to IR, regardless of viral status.IR induced apoptosis in p53 WT MCCP cells and growth arrest in p53 WT MCCN cells. In addition, p53 WT MCCP cell lines exhibited higher levels of homologous recombination repair than p53 mutant MCCN cells. By contrast, p53 mutant MCCN cells favored repair by nonhomologous end joining. These results indicate that sensitivity to IR is determined by p53status, and that double strand break pathway choice is associated with viral status in MCC cells.

ISBN: 9798357575753Subjects--Topical Terms:

642304
Virology.
Subjects--Index Terms:

Merkel cell carcinoma

Molecular Determinants of Radiosensitivity in Merkel Cell Carcinoma.
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520 $a Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two etiologies. Polyomavirus-associated MCC (MCCP) is caused by clonal integration of Merkel cell polyomavirus into host DNA. MCCP tumors typically have few mutations and often contain wild type (WT) p53. Nonviral MCC (MCCN) is caused by excessive exposure to ultraviolet radiation from sunlight and frequently harbors mutations in the p53 tumor suppressor. Despite their distinct etiologies, MCCP and MCCN tumors have similar histologic and clinical features and treatment strategies. For example, localized MCC is typically managed by surgical excision of the primary tumor and draining lymph nodes, followed by adjuvant radiation therapy. Inoperable tumors are treated with radiation therapy alone, as MCC is a highly radiosensitive cancer. Radiation therapy alone leads to similar survival rates as observed inpatients treated with surgery. Despite these similarities, MCCN behaves more aggressively than MCCP with an increased risk of disease progression, recurrence, and death. Viral status is not routinely considered when deciding on a course of treatment and it is not known if there are intrinsic differences in MCCP and MCCN radiosensitivity. To test this, we characterized the response to radiation in MCC cell lines with different viral and p53 statuses. We observed that loss of p53 function rendered MCC resistant to IR, regardless of viral status.IR induced apoptosis in p53 WT MCCP cells and growth arrest in p53 WT MCCN cells. In addition, p53 WT MCCP cell lines exhibited higher levels of homologous recombination repair than p53 mutant MCCN cells. By contrast, p53 mutant MCCN cells favored repair by nonhomologous end joining. These results indicate that sensitivity to IR is determined by p53status, and that double strand break pathway choice is associated with viral status in MCC cells.
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