PMID- 28486781
OWN - NLM
STAT- MEDLINE
DCOM- 20170915
LR  - 20190115
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 141
IP  - 4
DP  - 2017 Aug 15
TI  - Genomic analysis of inherited breast cancer among Palestinian women: Genetic
      heterogeneity and a founder mutation in TP53.
PG  - 750-756
LID - 10.1002/ijc.30771 [doi]
AB  - Breast cancer among Palestinian women has lower incidence than in Europe or North
      America, yet is very frequently familial. We studied genetic causes of this
      familial clustering in a consecutive hospital-based series of 875 Palestinian
      patients with invasive breast cancer, including 453 women with diagnosis by age
      40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt
      ("discovery series"); and 422 women diagnosed after age 40 and with negative
      family history ("older-onset sporadic patient series"). Genomic DNA from women in
      the discovery series was sequenced for all known breast cancer genes, revealing a
      pathogenic mutation in 13% (61/453) of patients. These mutations were screened in
      all patients and in 300 Palestinian female controls, revealing 1.0% (4/422)
      carriers among older, nonfamilial patients and two carriers among controls. The
      mutational spectrum was highly heterogeneous, including pathogenic mutations in
      11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, 
      PTEN and XRCC2. BRCA1 carriers were significantly more likely than other patients
      to have triple negative tumors (p = 0.03). The single most frequent mutation was 
      TP53 p.R181C, which was significantly enriched in the discovery series compared
      to controls (p = 0.01) and was responsible for 15% of breast cancers among young 
      onset or familial patients. TP53 p.R181C predisposed specifically to breast
      cancer with incomplete penetrance, and not to other Li-Fraumeni cancers.
      Palestinian women with young onset or familial breast cancer and their families
      would benefit from genetic analysis and counseling.
CI  - (c) 2017 UICC.
FAU - Lolas Hamameh, Suhair
AU  - Lolas Hamameh S
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
AD  - Medical Genetics Institute, Share Zedek Medical Center, and Faculty of Medicine, 
      Hebrew University, Jerusalem, Israel.
FAU - Renbaum, Paul
AU  - Renbaum P
AD  - Medical Genetics Institute, Share Zedek Medical Center, and Faculty of Medicine, 
      Hebrew University, Jerusalem, Israel.
FAU - Kamal, Lara
AU  - Kamal L
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
FAU - Dweik, Dima
AU  - Dweik D
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
FAU - Salahat, Mohammad
AU  - Salahat M
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
FAU - Jaraysa, Tamara
AU  - Jaraysa T
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
FAU - Abu Rayyan, Amal
AU  - Abu Rayyan A
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
FAU - Casadei, Silvia
AU  - Casadei S
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - Mandell, Jessica B
AU  - Mandell JB
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - Gulsuner, Suleyman
AU  - Gulsuner S
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - Lee, Ming K
AU  - Lee MK
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - Walsh, Tom
AU  - Walsh T
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - King, Mary-Claire
AU  - King MC
AUID- ORCID: 0000-0001-9426-1743
AD  - Departments of Medicine (Medical Genetics) and Genome Sciences, University of
      Washington, Seattle, WA.
FAU - Levy-Lahad, Ephrat
AU  - Levy-Lahad E
AD  - Medical Genetics Institute, Share Zedek Medical Center, and Faculty of Medicine, 
      Hebrew University, Jerusalem, Israel.
FAU - Kanaan, Moein
AU  - Kanaan M
AD  - Hereditary Research Laboratory and Department of Life Sciences, Bethlehem
      University, Bethlehem, Palestine.
LA  - eng
GR  - R01 CA157744/CA/NCI NIH HHS/United States
GR  - R01 CA175716/CA/NCI NIH HHS/United States
GR  - R35 CA197458/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170519
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - Breast Cancer, Familial
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Arabs/*genetics
MH  - Breast Neoplasms/*genetics/pathology
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Heterogeneity
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Sequence Analysis, DNA/*methods
MH  - Tumor Suppressor Protein p53/*genetics
PMC - PMC5526459
MID - NIHMS875320
OTO - NOTNLM
OT  - *BRCA1
OT  - *BRCA2
OT  - *Palestine
OT  - *TP53
OT  - *breast cancer
EDAT- 2017/05/10 06:00
MHDA- 2017/09/16 06:00
CRDT- 2017/05/10 06:00
PHST- 2016/12/29 00:00 [received]
PHST- 2017/03/24 00:00 [revised]
PHST- 2017/04/25 00:00 [accepted]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2017/09/16 06:00 [medline]
PHST- 2017/05/10 06:00 [entrez]
AID - 10.1002/ijc.30771 [doi]
PST - ppublish
SO  - Int J Cancer. 2017 Aug 15;141(4):750-756. doi: 10.1002/ijc.30771. Epub 2017 May
      19.