Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer

Andrea Prodosmo, Amelia Buffone, Manlio Mattioni, Agnese Barnabei, Agnese Persichetti, Aurora De Leo, Marialuisa Appetecchia, Arianna Nicolussi, Anna Coppa, Salvatore Sciacchitano, Carolina Giordano, Paola Pinnarò, Giuseppe Sanguineti, Lidia Strigari, Gabriele Alessandrini, Francesco Facciolo, Maurizio Cosimelli, Gian Luca Grazi, Giacomo Corrado, Enrico Vizza & 2 others Giuseppe Giannini, Silvia Soddu

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2 Citations (Scopus)

Abstract

Background: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Methods: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. Results: A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. Conclusions: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

Original languageEnglish
Article number135
JournalJournal of Experimental and Clinical Cancer Research
Volume35
Issue number1
DOIs
Publication statusPublished - Sep 6 2016

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Breast Neoplasms
Thyroid Neoplasms
Ovarian Neoplasms
Blood Cells
Neoplasms
Costs and Cost Analysis
Neoplasm Genes
Heterozygote
Lung Neoplasms
Colon
Cardiovascular Diseases
Population

Keywords

  • ATM cancer susceptibility gene
  • BRCA1/2
  • Early-onset breast cancer
  • p53-mitotic centrosomal localization (p53-MCL)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{868c7e9e70b0494cac9250a509efa557,
title = "Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer",
abstract = "Background: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Methods: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. Results: A total of seven individuals with ATM variants were identified, 5/65 (7.7 {\%}) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 {\%}) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. Conclusions: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.",
keywords = "ATM cancer susceptibility gene, BRCA1/2, Early-onset breast cancer, p53-mitotic centrosomal localization (p53-MCL)",
author = "Andrea Prodosmo and Amelia Buffone and Manlio Mattioni and Agnese Barnabei and Agnese Persichetti and {De Leo}, Aurora and Marialuisa Appetecchia and Arianna Nicolussi and Anna Coppa and Salvatore Sciacchitano and Carolina Giordano and Paola Pinnar{\`o} and Giuseppe Sanguineti and Lidia Strigari and Gabriele Alessandrini and Francesco Facciolo and Maurizio Cosimelli and Grazi, {Gian Luca} and Giacomo Corrado and Enrico Vizza and Giuseppe Giannini and Silvia Soddu",
year = "2016",
month = "9",
day = "6",
doi = "10.1186/s13046-016-0410-3",
language = "English",
volume = "35",
journal = "Journal of Experimental and Clinical Cancer Research",
issn = "0392-9078",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer

AU - Prodosmo, Andrea

AU - Buffone, Amelia

AU - Mattioni, Manlio

AU - Barnabei, Agnese

AU - Persichetti, Agnese

AU - De Leo, Aurora

AU - Appetecchia, Marialuisa

AU - Nicolussi, Arianna

AU - Coppa, Anna

AU - Sciacchitano, Salvatore

AU - Giordano, Carolina

AU - Pinnarò, Paola

AU - Sanguineti, Giuseppe

AU - Strigari, Lidia

AU - Alessandrini, Gabriele

AU - Facciolo, Francesco

AU - Cosimelli, Maurizio

AU - Grazi, Gian Luca

AU - Corrado, Giacomo

AU - Vizza, Enrico

AU - Giannini, Giuseppe

AU - Soddu, Silvia

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Background: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Methods: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. Results: A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. Conclusions: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

AB - Background: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Methods: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. Results: A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. Conclusions: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

KW - ATM cancer susceptibility gene

KW - BRCA1/2

KW - Early-onset breast cancer

KW - p53-mitotic centrosomal localization (p53-MCL)

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U2 - 10.1186/s13046-016-0410-3

DO - 10.1186/s13046-016-0410-3

M3 - Article

VL - 35

JO - Journal of Experimental and Clinical Cancer Research

JF - Journal of Experimental and Clinical Cancer Research

SN - 0392-9078

IS - 1

M1 - 135

ER -