Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships

Molecular Oncology - Tập 10 - Trang 360-370 - 2016
Rita A. Sakr1, Michail Schizas1, Jose V. Scarpa Carniello1, Charlotte K.Y. Ng2, Salvatore Piscuoglio2, Dilip Giri2, Victor P. Andrade1, Marina De Brot1, Raymond S. Lim2, Russell Towers1, Britta Weigelt2, Jorge S. Reis-Filho2,3, Tari A. King1
1Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
3Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States

Tóm tắt

Purpose: Lobular carcinoma in situ (LCIS) has been proposed as a non‐obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing.Methods: DNA samples extracted from microdissected LCIS, ILC and matched normal breast tissue or peripheral blood from 30 patients were subjected to massively parallel sequencing targeting all exons of 273 genes, including the genes most frequently mutated in breast cancer and DNA repair‐related genes. Single nucleotide variants and insertions and deletions were identified using state‐of‐the‐art bioinformatics approaches.Results: The constellation of somatic mutations found in LCIS (n = 34) and ILC (n = 21) were similar, with the most frequently mutated genes being CDH1 (56% and 66%, respectively), PIK3CA (41% and 52%, respectively) and CBFB (12% and 19%, respectively). Among 19 LCIS and ILC synchronous pairs, 14 (74%) had at least one identical mutation in common, including identical PIK3CA and CDH1 mutations. Paired analysis of independent foci of LCIS from 3 breasts revealed at least one common mutation in each of the 3 pairs (CDH1, PIK3CA, CBFB and PKHD1L1).Conclusion: LCIS and ILC have a similar repertoire of somatic mutations, with PIK3CA and CDH1 being the most frequently mutated genes. The presence of identical mutations between LCIS–LCIS and LCIS–ILC pairs demonstrates that LCIS is a clonal neoplastic lesion, and provides additional evidence that at least some LCIS are non‐obligate precursors of ILC.

Tài liệu tham khảo

10.1186/bcr3222 10.1038/nature11154 Berx G., 1996, E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain, Oncogene, 13, 1919 10.1007/s00428-001-0541-5 10.1038/nature11412 10.1158/0008-5472.CAN-09-1133 10.1158/1078-0432.CCR-12-1785 10.1016/j.jmoldx.2014.12.006 10.1371/journal.pone.0046688 10.1038/nbt.2514 Ciriello G., 2014, Abstract S2-04: Comprehensive molecular characterization of invasive lobular breast tumors, Cancer Res, 75, S2 10.1016/j.cell.2015.09.033 10.1097/PAS.0b013e3182918a2b 2012 Cancer Res San Antonio TX M. De Brot V.P. Andrade M. Morrogh M.F. Berger H.H. Won M.S. Koslow L.-X. Qin D.D. Giri N. Olvera R.A. Sakr T.A. King Novel Mutations in Lobular Carcinoma in Situ (LCIS) as Uncovered by Targeted Parallel sequencing. Thirty-fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9 10.1093/bioinformatics/btr629 10.1002/ijc.1208 10.1038/nature11143 Foote F.W., 1941, Lobular carcinoma in situ: a rare form of mammary cancer, Am. J. Pathol, 17 10.1038/nrc1299 10.1126/scisignal.2004088 10.1002/1097-0142(197808)42:2<737::AID-CNCR2820420247>3.0.CO;2-T 10.1002/cncr.20273 10.1038/nature12634 10.1101/gr.129684.111 Lakhani S.R., WHO Classification of Breast Tumors 10.1016/j.ejca.2006.03.019 10.1136/mp.48.2.M74 10.1093/bioinformatics/btr665 10.1038/nature12912 10.1093/bioinformatics/btp324 10.1186/s13058-015-0580-5 10.1111/j.1365-2559.2010.03568.x 10.1186/s13059-014-0484-1 10.1002/gcc.20368 10.1101/gr.107524.110 10.1007/s00428-006-0192-7 10.1002/path.4325 10.1016/0046-8177(91)90105-X 10.1136/mp.54.2.91 10.1038/nbt.1754 10.1158/0008-5472-CAN-04-3913 10.1158/1078-0432.CCR-13-2267 10.1038/nmeth0810-575 10.1002/humu.22225 10.1158/0008-5472.CAN-07-6854 10.1038/nature11017 10.1038/bjc.1997.523 10.1158/2159-8290.CD-11-0184 10.1309/AJCP7AK1VWFNMCSW 10.1038/ng.3096
Thông tin
Thông tin xuất bản

Molecular Oncology

Tập 10

360-370

Thông tin tác giả